Dietary fibers regulate intestinal barrier function; however, the precise mechanisms remain unclear. This study investigated the effects of psyllium fibers on antimicrobial protein expression, focusing on the type II immunity and tuft cell-group 2 innate lymphoid cell (ILC2) circuit in the small intestine of the mouse. Supplemental psyllium fiber upregulated antimicrobial proteins, such as small proline-rich protein 2A (SPRR2A) and resistin-like beta (RELMβ), in mouse small intestine, evidently affecting cecal microbiota composition. Psyllium fibers also increased the RNA and protein expression of molecules related to ILC2 and tuft cells, such as IL-13, IL-25, DCLK1, Gfi-1b, SH2 domain-containing protein 3C, and Spi-B. In addition, ILC2 inhibitor (disulfiram) and bitter taste receptor blocker administration reduced psyllium-induced SPRR2A and RELMβ expression. Collectively, psyllium supplementation upregulates antimicrobial proteins such as SPRR2A and RELMß via the type II immune response and tuft cell-ILC2 circuit in the mouse small intestine.

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients (n=160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott). In addition to comparing clinical evaluation and prescription rates with either usual care or with testing, patients and staff completed a questionnaire about their experience of molecular POCT in primary care. The immediate availability of the result was important to patients (100%) and staff (≈90%) stated that molecular testing improved quality of care. Interestingly, only 22.73% of patients with a Centor score >2 tested positive for Strep A and overall, less than 50% of Centor scores 3 and 4 tested positive for Strep A with the ID NOW testing platform. The addition of rapid molecular POCTs to clinical assessment resulted in a 55- 65% reduction in immediate and deferred antibiotic prescriptions. The intervention was popular with patients and medical staff but was associated with increased cost and a longer appointment length.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

Zinc nanoparticles (ZnNPs) open new opportunities for biomedical applications as a strategy against microbes and dye removal in an efficient way. The composite ZnNPs using Rhododendron arboreum (R. arboreum) stem bark were synthesized and characterized for UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized nanoparticles showed zones of inhibition of 23±0.09, 18±0.1 and 16±0.05 mm, against the Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against K. pneumoniae, S. aureus, and E. coli were found to be 34±0.21 and 72.71±0.47, 47±0.11 and 94.86±0.84 and 94±0.18 and 185.43±0.16 µg/mL, respectively. The biosynthesized ZnNPs resulted in significant eradication of the outer and inner membranes of the bacterial cells. Likewise, the synthesized ZnNPs showed time-dependent photocatalytic degradation activity and revealed 65% methyl orange dye degradation with an irradiation period of 6 hours. The findings of this study suggest the suitability of the novel R. arboreum stem bark-based ZnNPs as an effective ameliorant against bactericidal activities and photocatalysts for the removal of hazardous water contaminants.

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation of the methanol extract of this strain’s culture broth led to the discovery of three new pyranone derivatives fallopiaxylaresters A-C (1–3) and a new bisabolane-type sesquiterpenoid named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously-reported pestalotiopyrone M (5). Known pyranone derivatives (6–11), sesquiterpenoids (12–14), isocoumarin derivatives (15–17), and an aromatic allenic ether (18) were co-isolated. Their structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy and quantum chemical computation method. The antimicrobial, anti-inflammatory, and α-glucosidase inhibitory activities of selected compounds and crude extract were evaluated in vitro. The extract inhibited nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 μg/mL. The compounds 5, 7 and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 μM.

The purpose of this study was to identify candidate novel species performing beneficial ecological functions from soil. The hypothesis was that novel culturable species with antibiotic production potential could be readily found from soil in the Nature Canyon at Los Angeles Pierce College. 137 bacterial isolates from soil were grown on nutrient agar, ISP-6 medium, or LB agar and partial 16S was ascertained using the Sanger platform for regions V1-V4. One of the potentially novel isolates, Pseudomonas sp. 21-C3-ER, was isolated on nutrient agar from fallow soil in an agricultural nature preserve in Los Angeles. The soil conditions were 3.7% moisture, clay texture by touch, 13.37% organic matter, pH=6.63, TDS=638, 150 ppm nitrogen, 114 ppm phosphate, and 42 ppm potash. Whole genome sequencing was performed on the DNBseq platform and species identification was performed with TRUEBacID; the closest relative was Pseudomonas brassicacearum subsp. neoaurantiaca which was 92.05% similar by genomic evidence. 197 virulence factors were identified including flagellar biosynthesis, motor proteins, Beta-lactamase, Fosfomycin, copper, and sulfur drug resistance. Gram stain of strain 21-C3-ER revealed gram negative rods. Rods were visualized with scanning electron microscopy, revealing individuals approximately 1 µm in length. Secondary metabolite analysis using antiSMASH showed a variety of post-translationally modified proteins and a promysalin analog. The qualitative test for pyoverdine siderophore production using UV light was positive. Metabolic analysis using RAST indicated genes were present for pyoverdine production, antimicrobial resistance, and ammonification. The nitrate reduction test was positive. Denitrifying bacteria may prevent leaching of nitrates from soil, since ammonia has a higher affinity to soil and organic matter than nitrate. We propose Pseudomonas fernandeno as a novel species. The type stain is 21-C3-ER.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

This study evaluated the stability of the Poly-(sorbitol-co-citrate adipate) with potential applica-tion in the biomedical area. Thus, the physical, chemical and microbiological stability of this was investigated. First, the chemical stability in alkaline phosphate buffer (pH 7.4) was evaluated for 5 days. In aqueous solution, the copolymer acidified the medium indicating the presence of residual citric acid. In the moisture absorption test the results obtained followed the pH, reinforcing the presence of citric acid. In the evaluation of the antimicrobial activity the results indicate that the copolymer did not allow the growth of the yeast Saccharomyces cerevisiae, as the only source of carbon. However, in the cell lysis phase and due to the restriction of access to nutrients in the culture medium, the copolymer showed a loss of mass due to its use by the microorganism. Thus, it presented biodegradability property under extreme conditions of cell culture.

This review delves into using natural antimicrobials in the dairy industry and examines various sources of these compounds, including microbial, plant, and animal sources. It highlights dairy products' most commonly used natural antimicrobials, such as nisin, lysozyme, lactoferrin, chitosan, and essential oils. It discusses the mechanisms by which they inhibit microbial growth and improve the shelf life of dairy products. Moreover, the review explores encapsulation technology as a promising approach for increasing the viability of natural antimicrobials. It discusses how encapsulation technology can protect these compounds from environmental factors that can reduce their effectiveness, such as pH, temperature, and oxygen exposure. The review also highlights the different materials that can be used for encapsulation, such as alginate, chitosan, and starch, and discusses their properties and suitability for encapsulating different natural antimicrobials. Finally, the review examines the benefits and challenges of using natural antimicrobials in dairy products. While natural antimicrobials offer several advantages, including improved safety, quality, and sensory properties of dairy products, it's crucial to be aware of the challenges associated with their use, such as potential allergenicity, regulatory requirements, and consumer perception. The review concludes by emphasizing the need for further research to identify and develop effective and safe natural antimicrobials for the dairy industry to ensure the quality and safety of dairy products for consumers.

Bacterial infections and resistance to antibiotic drugs represent the highest challenges to public health. The search for new and promising compounds with anti-bacterial activity is a very urgent matter. In order to promote the development of platforms enabling to the discovery of compounds with anti-bacterial activity, Fourier Transformed Mid-Infrared (FT-MIR) spectroscopy associated with the machine learning algorithms were used to predict the impact of compounds extracted from Cynara cardunculus against Escherichia coli cells. According to the plant tissue (seeds, dry and fresh leaves, and flowers) and the solvents (ethanol, methanol, acetone, ethyl acetate, and water), compounds with different compositions concerning, phenol content, antioxidant, and antimicrobial activity were obtained. Principal component analysis of spectra, allowed to discriminate compounds that inhibit the E. coli growth, according to the conventional assay. The supervised classification models enabled the prediction of the compound's impact on the E. coli growth, with the accuracy for the test data: Partial least squares-discriminant analysis of 94%; Support vector machines of 89%; k-Nearest neighbor of 72%; and a Backpropagation network of 100%. According to the promising results, the integration of FT-MIR spectroscopy with machine learning presents a high potential to promote the discovery of new compounds with antibacterial activity, thereby streamlining the drug exploratory process.

Abstract: The study used whole-genome sequencing (WGS) and bioinformatics analysis for the genomic characterization of 60 isolates of Listeria monocytogenes isolated from cattle farms, cattle abattoirs, and retail outlets in Gauteng province, South Africa. The isolates' sequence types (STs), clonal complexes (CCs), and lineages were determined using in silico multilocus sequence typing (MLST). We used BLAST-based analyses to identify virulence and antimicrobial genes, plasmids, proviruses, and the CRISPR-Cas system. The study investigated any association of the detected genes to the origin in the beef production chain of the L. monocytogenes isolates. Overall, in 60 isolates of Listeria monocytogenes, there were 7 STs, 6 CCs, 44 putative virulence factors, 2 resistance genes, 1 plasmid with AMR genes and 3 with conjugative genes, 1 CRISPR gene, and all 60 isolates were positive for proviruses. Among the 7 STs detected, ST204 (46.7%) and ST2 (21.7%) were the most prominent, with ST frequency varying significantly (p<0.001). The predominant CC detected were CC2 (21.7%) and CC204 (46.7%) in lineages I and II, respectively. Of the 44 virulence factors detected, 26 (across Listeria Pathogenicity Islands, LIPIs) were present in all the isolates. The difference in the detection frequency varied significantly (P<0.001). The two AMR genes (fosX and vga(G)) detected were present in all 60 (100%) isolates of L. monocytogenes. The only plasmid, NF033156, was present in 3 (5%) isolates. A CRISPR-Cas system was detected in 6 (10%), and all the isolates carried proviruses. Significant differences were detected in the frequencies of STs and virulence factors regarding the source and sample type of the L. monocytogenes isolates. The presence of both fosX and vga(G) genes in all the isolates from the three industries (cattle farms, abattoirs, and retail outlets) can potentially cause therapeutic implications. Our study, which characterized L. monocytogenes recovered from the three levels in the beef production chain in the country, provides the first evidence of the distribution of the pathogen with potential food safety and therapeutic implications.

Abstract: Colistin is a last-resort antimicrobial for treating multidrug-resistant Gram-negative bacteria. Phe-notypic colistin resistance is highly associated with plasmid-mediated mobile colistin resistance (mcr) genes. mcr-bearing Enterobacteriaceae have been detected in many countries, with the emergence of colistin-resistant pathogens a global concern. This study assessed the distribution of mcr-1, mcr-2, mcr-3, mcr-4, and mcr-5 genes with the phenotypic colistin resistance in isolates from diarrheal infants and children in Bangladesh. Bacteria were identified using the API-20E biochemical panel and 16s rDNA gene sequencing. Polymerase chain reac-tions detected mcr gene variants in the isolates. Their susceptibilities to colistin were determined by agar dilu-tion and E-test by minimal inhibitory concentration (MIC) measurements. Over 30.0% (69/225) of isolates showed colistin resistance by agar dilution assessment (MIC> 2.0 μg/mL). Overall, 15.5% of isolates carried mcr genes (7, mcr-1; 17, mcr-2; 13, mcr-3; and co-occurrence occurred in 2 isolates). Clinical breakout MIC val-ues (≥ 4 μg/mL) were associated with 91.3% of mcr-positive isolates. The mcr-positive pathogens include twenty Escherichia spp., five Shigella flexneri, five Citrobacter spp., two Klebsiella pneumoniae, and three Pseudo-monas parafulva. mcr-genes appeared to be significantly associated with phenotypic colistin resistance phe-nomena (p=0.000), with 100% colistin-resistant isolates showing MDR phenomena. Age and sex of patients showed no significant association with detected mcr variants. Overall, mcr-associated colistin-resistant bacte-ria have emerged in Bangladesh, which warrants further research to determine their spread and instigate ac-tivities to reduce resistance.

Abstract: The Willows, belonging to the genus Salix, encompass a vast array of species and hybrids, totaling between 330 to 500 species along with approximately 200 hybrids. These plants are found across continents such as Africa, North America, Europe, and Asia, exhibiting diverse forms ranging from trees to shrubs and prostrate plants. Traditionally, Willows have been utilized in folk medicine due to their rich reservoir of biologically active compounds, with salicin being a notable example, serving as a prodrug for salicylic acid.The chemical composition of Willows is highly diverse, with 322 secondary metabolites identified thus far. These include various classes such as flavonoids (94 types encompassing flavonols, flavones, flavanones, isoflavones, flavan-3-ols like catechins and procyanidins, chalcones, dihydrochalcone, anthocyanins, and dihydroflavonols), phenolic glycosides (76), organic acids (28), non-phenolic glycosides (17), sterols, and terpenes (17), simple phenolics (13), lignans (7), as well as volatiles and fatty acids (69). This rich chemical di-versity underpins the various pharmacological activities exhibited by Willows. The pharmacological properties attributed to Willows are extensive and include analgesic, an-ti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective, and hepatoprotective effects. These properties make Willows a subject of con-siderable interest in the fields of medicine and pharmacology. In summary, Willows represent a valuable natural resource with a diverse chemical composition and a wide range of pharmacological activities. This study aimed to enhance our comprehension of the medicinal characteristics of willow bark extract, focusing on its antimicrobial properties. This investigation holds significance in validating the traditional usage of willow bark and investi-gating its potential utility in contemporary medicine.

Due to bacterial contamination, natural medicinal preservatives may be an alternative to enhance the quality of milk. Besides, thorough biocompatibility testing is deemed essential before integrating natural extracts into food products. To address this matter, our research focused on evaluating the antimicrobial potential of Plectranthus amboinicus, Flueggea leucopyrus, Cymbopogon citratus, and Bacopa monnieri against prevalent foodborne pathogens, including Staphylococcus aureus, Escherichia coli, Salmonella spp, and Pseudomonas aeruginosa and investigating the efficacy of plant extracts as natural preservatives along with biocompatibility and toxicity assessments. The methanolic extracts of plant materials were used for measuring antimicrobial activity using the agar well diffusion method, Minimum Inhibitory Concentration (MIC) and Minimum bactericidal concentration (MBC) assays. The preservative activity was tested by isolating pathogenic organisms in a sterilized milk medium and toxicity and biocompatibility was assessed using zebrafish embryo and brine shrimp lethality assays. At a concentration of 400 mg/ml, all plant extracts demonstrated notable activity against bacterial strains. B. monnieri at 400 mg/ml exhibited particularly significant effects on S. aureus (30.3 mm ± 0.6), surpassing the positive control, gentamicin (28.3 mm ± 0.6), while also displaying pronounced activity against E. coli. F. leucopyrus, at the same concentration, showed antimicrobial activity comparable to the positive control against both S. aureus (28.0 mm ± 1.0) and E. coli (27.0 mm ± 1.0). However, as there’s weak-mild toxicity in these herbs, prior to consumption, careful consideration of their toxicity and biocompatibility is imperative for ensuring their safe use.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

Biological Activities of ethanol extracts of Hericium erinaceus obtained as a result of optimization analysis

Research on titanium oxo complexes (TOCs) are usually focused on their structure and photocatalytic properties. Findings from these investigations spurred our interest in exploring also their potential biological activities. In this study, we focused on the synthesis and structure of a compound with the general formula [Ti8O2(OiPr)20(man)4] (1), which was isolated from the reaction mixture of titanium(IV) isopropoxide with mandelic acid (Hman) in a molar ratio of 4:1. The structure (1) was determined using single-crystal X-ray diffraction, while spectroscopic studies provided insights into its physicochemical properties. To assess the potential practical applications of (1), its microcrystals were incorporated into a polymethyl methacrylate (PMMA) matrix, yielding composite materials of the type PMMA + (1) (2 wt.%, 5 wt.%, 10 wt.%, and 20 wt.%). The next stage of our research involved the antimicrobial activity evaluation of the obtained materials. Investigations carried out demonstrated antimicrobial activity of pure (1) and its composites (PMMA + (1)) against both Gram-positive and Gram-negative strains. Furthermore, MTT tests conducted on the L929 murine fibroblast cell line confirmed the lack of cytotoxicity of these composites. Our study identified (1) as a promising antimicrobial agent, also for producing composite coatings.

C. auris is a newly emerging yeast, raising public health concerns due to its outbreak potential, lack of protocols for decontamination and isolation of patients or contacts, increased resistance to common antifungals and associated high mortality. This research aimed to describe the challenges related to identifying the outbreak, limiting further contamination, and treating affected individuals. We retrospectively analysed all cases of C. auris detected between October 2022 and August 2023, but our investigation focused on a three-month-long outbreak in the department of cardio-vascular surgery and the related intensive care unit. Along with isolated cases in different wards, we identified 13 patients who became infected or colonized in the same area and time, even though the epidemiological link could be traced only in 10 patients, according to the epidemiological investigation. In conclusion, our study emphasizes the substantial challenge encountered in clinical practice when attempting to diagnose and limit the spread of an outbreak. Therefore, it is crucial to promptly apply contact precaution measures and appropriate environmental cleaning, from the first case detected positive.

Neonatal sepsis is a leading cause of morbidity and mortality in neonates, particularly in low and middle-income countries. The emergence of antimicrobial resistance is a rapidly growing global problem. A significant proportion of the pathogens that commonly cause neonatal sepsis are resistant to multiple antibiotics. Therefore, for the empirical treatment of neonatal sepsis, the repurposing of older antibiotics that are effective against multidrug-resistant pathogens is being investigated. This review aims to provide an overview of current research and experience using the repurposed antibiotics, Colistin and Fosfomycin, for the empirical treatment of neonatal sepsis. Based on current knowledge, Colistin and Fosfomycin may be potentially helpful for the empirical treatment of sepsis in neonates due to their efficacy against a wide range of pathogens and acceptable safety profile.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

The use of Lactic Acid Bacteria (LAB) for probiotic enrichment of minimally processed fruit is a well-established practice in literature. In addition, several LAB demonstrated a strain-specific ability to control harmful microorganisms and decay agents, improving shelf-life, maintaining quality and promoting the safety of fruits and vegetables. Edible coatings can help modulate phenomena of gas exchange and water loss by fruits, representing protection from physical damage and spoilage phenomena linked to oxidation and the development of undesired microorganisms. At the same time, the coating can represent an innovative delivery matrix for the LAB strains of potential interest to improve safety and quality in the postharvest management of fruits. In this work, five Lactiplantibacillus plantarum strains, previously characterized for their probiotic and antifungal activity, have been incorporated into a sodium alginate coating to develop edible probiotic coatings with antifungal properties for table grapes cv. Italia. The transfer of probiotics and their survival were evaluated by comparing coated and uncoated table grapes during 14 days of cold storage at 4 °C. The alginate edible coating increased the number of probiotics transferred to the surface of the berries from about 5 to more than 7 Log CFU/g, with a crucial impact on the potential functional attributes of the final product. The ability of the functionalised coatings to counteract the decay development was evaluated on table grapes berries artificially contaminated with Aspergillus niger CECT 2805. A significant reduction of lesion diameter was observed in alginate coating with L. plantarum 11-A. The lesion diameter reduction was also accompanied by the reduction of the symptoms of infection, such as browning around the wound. These results suggest the application of selected strains of L. plantarum as promising bio-resources to enhance the overall value of ready-to-eat fruits and vegetables, particularly in combination with edible coating as a carrier matrix. While a strain-dependent effect was not detected with respect to the improvement of the number of cells in the edible coating, a variability depending on the biotype used was detected for the properties linked to biocontrol, suggesting that the inclusion in edible packaging may represent an innovative criterion in the selection of lactobacilli to be applied postharvest.

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

The present work was aimed at the chemical characterization and antimicrobial activity of some extracts of aerial parts (essential oils from leaves and inflorescences, and resins from inflorescences) of two legal hemp (Cannabis sativa) varieties, Tisza and Kompolti, grown in Sardinia. Chemical characterization was carried out by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. The antimicrobial activity of these extracts against a panel of microorganisms was also determined via minimum inhibitory concentration (M.I.C.) determination. While the results showed a minor or negligible antimicrobial activity of the extracts against Gram+ and Candida strains, a good antibacterial activity (especially of resins) was recorded against S. aureus; no substantial differences were detected between of the chemical compositions of the two Cannabis varieties.

Simple Summary: The distribution of typical bacterial redox enzymes such as pyruvate-ferredoxin oxidoreductase (PFOR) in protozoa remains interestingly puzzling. Previous studies have demonstrated diverse cellular localizations of PFOR in some amitochondriate anaerobic protozoa. PFOR is of particular pharmacological importance because it catalyzes the reductive bio-activation of nitro-based prodrugs to cytotoxic radical metabolites. Metronidazole was developed primarily as an antiprotozoal agent against infections caused by Trichomonas vaginalis. However, its antimicrobial spectrum was subsequently expanded to cover anaerobic bacterial infections. It has been shown that mutations in the genes encoding PFOR result in inherent resistance of PFOR-possessing anaerobic protozoa and bacteria to nitro-based prodrugs. Deciphering the evolutionary history of PFOR is crucial in deepening our understanding of the evolution of anaerobic pathogens and unfold new approaches for drug discovery and targeting in pathogen chemotherapy. Abstract: The present frontrunners in the chemotherapy of infections caused by protozoa are nitro-based prodrugs that are selectively activated by PFOR-mediated redox reactions. This study seeks to analyze the distribution of PFOR in selected protozoa and bacteria by applying comparative bioinformatics approaches to test the hypothesis that PFOR was most likely acquired through horizontal gene transfer (HGT) from bacteria. Furthermore, to identify other genes that were putatively acquired using proteome-wide and gene expression analyses. A plausible explanation for the patchy occurrence of PFOR in protozoa is based on the hypothesis that bacteria are potential sources of genes that enhance optimal adaptation of protozoa in hostile environments. The exclusively expressed proteins obtained from Entamoeba histolytica and the putative gene donor, Desulfovibrio vulgaris, showed an over-expression of eleven genes involved in intermediary metabolism. If these results can be reproduced in other PFOR-possessing protozoa, it would provide a more validated evidence to support the horizontal transfer of pfor from bacteria.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Globally increasing antibiotic resistance has been connected to the use of antibiotics in medical, veterinary, and agricultural medicine, contributing to the burden of antibiotic resistance in Asia and Europe. The main objective of this study was to correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. This study reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. Furthermore, in the environment and integrated studies, aminoglycosides and β-lactams is resistant. While in Germany, a high rate of AMR resistance in all three sectors was reported in β-lactam. However, E. coli was the most frequent pathogen in both countries and is highly resistant to β-lactam, followed by cephalosporin in all the compartments. Monitoring and evaluating antibiotic-sensitivity patterns and developing proper antibiotic regimens may lead to improved outcomes for inhibiting and controlling E. coli infections in various parts of the world.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, antioxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review provides a comprehensive overview of the multifaceted biological activities exhibited by T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed encompassing its role in combating a broad spectrum of bacterial and fungal pathogens, respectively. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the antioxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. Overall, this review consolidates the existing knowledge on T-4-ol, providing a holistic understanding of its pharmacological abilities. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications.

Chagas disease is a Neglected Tropical Disease with limited and ineffective therapy. In a search for new antitrypanosomal compounds, we investigated the potential of metabolites from bacteria living in corals and sediments of the Southeastern Brazilian coast. Three corals Tubastraea coccinea, Mussismilia hispida, Madracis decactis and sediments yielded 11 bacterial strains, that were fully identified by MALDI-ToF/MS or gene sequencing, resulting in six genera - Vibrio, Shewanella, Mesoflavibacter, Halomonas, Bacillus and Alteromonas. To conduct this study, EtOAc extracts were prepared and tested against Trypanosoma cruzi. Crude extracts showed IC50 values ranging from 15 to 51 μg/mL against trypomastigotes. The bacterium Mesoflavibacter zeaxanthinifaciens was selected for fractionation, resulting in an active fraction (FII) with IC50 values of 17.7 μg/mL and 23.8 μg/mL against the trypomastigotes and amastigotes, respectively, with neither mammalian cytotoxicity nor hemolytic activity. Using NMR and ESI-HRMS analysis, FII revealed the presence of unsaturated iso-type fatty acids. Its lethal action was investigated, leading to a protein spectral profile of the parasite altered after treatment. FII also induced a rapid permeabilization of the plasma membrane of the parasite, leading to cell death. These findings demonstrate these unsaturated iso-type fatty acids as possible new hits against T. cruzi.

Carbapenem antibiotics are the drug of choice for treating multidrug-resistant bacterial infections. Metallo-beta-lactamases (MBLs) are carbapenemase capable of hydrolyzing nearly all therapeutically available beta-lactam antibiotics. Consequently, a need to assess the frequency and phenotypic resistance phenomena of two MBL genes in diarrheal and urinary tract infections (UTIs). Samples were collected through a cross-sectional study, with MBLs genes detected via PCR. Two hundred twenty eight diarrheal bacteria were isolated from 240 samples. The most predominant pathogens were Escherichia coli (32%) and Klebsiella spp. (7%). Phenotypic resistance to amoxicillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 50.4%, 65.6%, 66.8%, 80.5%, 54.4%, 41.6%, 25.7%, 41.2%, 37.2%, and 42.9%, respectively.  Total 142 UTI pathogens were obtained from 150 urine samples, with Klebsiella spp. (39%) and Escherichia coli (24%) are the major pathogens. Phenotypic resistance to amoxycillin-clavulanic acid, aztreonam, cefuroxime, cefixime, cefepime, imipenem, meropenem, gentamicin, netilmicin, and amikacin was 93.7%, 75.0%, 91.5%, 93.7%, 88.0%, 72.5%, 13.6%, 44.4%, 71.1%, and 43%, respectively.  Twenty four diarrheal isolates carried either blaNDM-1 or blaVIM genes; the overall MBL gene prevalence was 10.5%. Thirty six UTI pathogens carried either blaNDM-1 or blaVIM genes (25.4%). Seven isolates carried both blaNDM-1 and blaVIM genes.  MBL genes exhibited a strong association with phenotypic carbapenem and other beta-lactam antibiotic resistance. Resistance to carbapenems requires active surveillance and stewardship.

Abstract: Brassinosteroids (BR) are essential plant hormones that play a crucial role in regulating plant growth and development, as well as their resistance to abiotic and biotic stresses, including pathogen infections. In the context of plant im-munity, BR influence various processes such as the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the re-inforcement of the plant cell structure. The aim of work is understand the role of BR in plant defense against abiotic and biotic stresses. BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, contributing to increased plant resistance to abiotic stresses. The study discusses various mechanisms of BR action on plant immunity, including the regulation of gene expression related to defense, activation of the plant defense system, in-teraction with other plant hormones, regulation of water and salt balance, and influence on photosynthetic processes. In the context of plant immunity, BR influence various processes, including the expression of genes related to pathogen defense, the production of antimicrobial compounds, and the reinforcement of the plant cell structure. Additionally, BR are involved in the regulation of metabolic processes, water economy, and photosynthesis, con-tributing to increased plant resistance to abiotic and biotic stresses. The paper emphasizes the importance of further research on the role and mechanisms of action of BR in plant immunity, which may contribute to the development of more effective strategies for the use of BR in agriculture, horticulture, and plant protection.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

The antimicrobial quantitative structure–activity relationship of plant flavonoids against Gram-positive bacteria was established in our previous works, and the cell membrane was confirmed as a major site of action. To investigate whether plant flavonoids have similar antibacterial effects and mechanisms against both Gram-negative and Gram-positive bacteria, here, the minimum inhibitory concentrations (MICs) of 37 plant flavonoids against Escherichia coli were determined using the microdilution broth method, and then the correlation between their lipophilic parameter ACD/LogP or LogD_7.40 value and their MIC was analyzed. Simultaneously, the correlation between the ACD/LogP or LogD_7.40 value and the MIC of 46 plant flavonoids reported in literature against E. coli was also analyzed. Both sets of results showed that there is a significant correlation between the LogP value and the MIC of plant flavonoids against Gram-negative bacteria. However, it is difficult to effectively predict the MIC of plant flavonoids against Gram-negative bacteria from their lipophilic parameters. By comparing two regression curves derived from plant flavonoids against Gram-negative and Gram-positive bacteria, it was further discovered that the antibacterial activities of most plant flavonoids against Gram-negative bacteria are stronger than those against Gram-positive bacteria when their LogP values are less than about 3.0, but the opposite is true when their LogP values are more than about 3.6. Moreover, this comparison also suggests that unlike mainly acting on the cell membrane of Gram-positive bacteria, plant flavonoids have multiple mechanisms against Gram-negative species, while the cell membrane is also an important action site among them. Combined with the correlation analyses between the enzyme inhibitory activity and the LogP value of the reported flavonoids, it was further suggested that DNA gyrase is another important target of plant flavonoids against Gram-negative bacteria.

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

Background: To compare photodynamic therapy 41 and the use of probiotics in reducing halitosis assessed through gas chromatography and microbiome analysis. Methods: Participants aged from 18 to 25 years, showing sulfide (SH2) ≥ 112 ppb on gas chromatography, were selected. They were divided into 4 treatment groups: Group 1 - Tongue Scraping; Group 2- Antimicrobial Photodynamic Therapy (aPDT); Group 3- Probiotics; Group 4- Antimicrobial Photodynamic Therapy (aPDT) and Probiotics. The halimetry process was performed before, immediately after the treatments, 7 days, 14 days and 30 days after the initial collection. The collections for later microbiological analysis were made along with the halimetry, for the microbiome analysis. Results: Treatment with aPDT or probiotics under these experimental conditions was not able to change the bacteria present in the biofilm of the tongue. Conclusions: More research is needed to know the behavior of the oral microbiome in the presence of halitosis and the effectiveness of new treatments.

Infections with multi-drug-resistant (MDR) pathogens in food-animals threaten public health and food security. However, the epidemiology and factors associated with MDR Escherichia coli on Ugandan farms are not well known. This study investigated the prevalence, resistance patterns and factors associated with MDR E. coli carriage on chicken farms. A total of 158 E. coli strains were isolated from 158 chicken farms. The disc diffusion method for susceptibility testing was performed. Clinical breakpoints were interpreted according to Clinical and Laboratory Standards Institute guidelines. MDR was defined as resistance to three or more classes of antimicrobials. MDR E. coli prevalence on chicken farms was 62.7% (95% CI: 55.0 – 70.3). High resistance was observed against ampicillin 79.8% (95% CI: 72.7–85.4), tetracycline 72.8% (95% CI: 65.2–79.2), cotrimoxazole 55.7% (95% CI: 47.8–63.3), and ciprofloxacin 38% (95% CI: 30.7–45.9). Farmers who were males (APR = 0.72, CI: 0.55, 0.93), and attained at least secondary education (APR=0.64, CI: 0.46, 0.88) and administration of recommended antibiotic doses (APR = 0.76, CI: 0.59–0.96) posed a lower risk of MDR E. coli carriage. Farms without footbaths posed a heighten risk (APR=1.48, CI: 1.16–1.88). MDR E. coli were highly prevalent on chicken farms. This study underscores the need for antimicrobial stewardship and improved infection prevention strategies on chicken farms.

Plant growth promoting rhizobacteria (PGPR) are a diverse group of microorganisms including genera such as Pseudomonas, Bacillus, Serratia, Enterobacter and Klebsiella. These bacteria have the ability to colonize roots externally and internally, and to directly enhance plant growth employing various mechanisms like phytohormone production and nutrient mineralization. These microbes can also promote plant growth indirectly by secreting antimicrobial compounds (e.g., siderophores, hydrogen cyanide) to antagonize root pathogens or by inducing defensive responses in the plant. Interestingly, there are also cases where production of antibiotic compounds such as 2,4-Diacetylphloroglucinol have the direct effect of enhancing plant growth and yield, irrespective of their biocontrol effects. The objective of this paper is to review publications showcasing PGPRs that have the capacity to both control root pathogens and stimulate plant growth, and to discuss what mechanisms might be involved.

In this study, we aimed to determine the trend of antimicrobial resistance pattern of pathogens isolated in samples collected from patients hospitalized in the intensive care unit (ICU), in selected periods before and after COVID-19. A retrospective study of bacterial pathogens was performed on 1267 patients. The resistance patterns were analyzed using Vitek 2 Compact system. Positive-bacterial culture data of 1695 samples from pre-COVID-19 period and 1562 from post-COVID-19 period were obtained. The most frequently isolated in both periods were Staphylococcus aureus and Klebsiella spp. Klebsiella spp. had a statistically significant increase in resistance rates in the post COVID-19 period, against colistin, gentamicin and aztreonam. For E. coli strains, it was registered a significant increase against colistin and a significant decrease against levofloxacin and imipenem. For Acinetobacter spp. strains it was observed a significant increase against colistin. More than 50% from the Staphylococcus aureus strains were MRSA with statistically significant increases in antimicrobial resistance rate in the post-COVID-19 period against doxycycline, linezolid, rifampicin and teicoplanin. The study revealed a significantly increasing trend of the antimicrobial resistance rate of Gram-negative pathogens (Klebsiella spp., Acinetobacter spp.) against certain antibiotics, including those used only in cases where there are no other therapeutic options.

Skin and soft-tissue infections (SSTI) are common cases of hospital-acquired infections with aetiologic agents exhibiting antimicrobial resistance (AMR). We determined the prevalence, proportion of laboratory-investigated cases, AMR-profiles, and factors associated with SSTI and multi-drug resistance (MDR). This study was based on archived data of patients suspected of SSTI from 2019-2021 at Jinja Regional Referral Hospital. The analysis involved 268 randomly selected patient reports. Prevalence of SSTI was 66.4%. Laboratory-investigated cases were 14.11%. Staphylococcus aureus (n=51) was the most isolated organism. MDR pathogens explained 47% of infections. Methicillin-resistant S. aureus was up to 44%. In addition, 61% of Gram-negatives had the potential to produce extended-spectrum beta-lactamases, while 27% were non-susceptible to carbapenems. Ward of admission was significantly associated with infection (aPR=1.78, 95% CI: 1.003-3.18, p-value=0.04). Age category (19-35) was an independent predictor for MDR infections (aPR=2.30, 95%CI:1.02-5.23, p-value=0.04). The prevalence is relatively high with MDR pathogens responsible for almost half of the infections. Routine use of culture and sensitivity testing should be done for proper infection management. Gentamicin and ciprofloxacin can be considered for empirical management of emergency SSTI suspected of S. aureus. Recognizing SSTI under the Global Antimicrobial resistance Surveillance System would lead to improved preparedness and response to AMR.

This study investigated the presence, distribution, and antimicrobial resistance profiles of extend-ed-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in a dairy herd located in Northern Italy. A questionnaire was administered, and the feces of clinically healthy pre-weaned dairy calves, their mothers, and the cows treated for mastitis, waste milk, water, and environmental samples, were collected and inoculated on Chromagar ESBL™ medium. The questionnaire identi-fied several risk factors including administration of waste milk to male calves, lack of routine cleaning of calf feeding and housing equipment, and blanket dry cow therapy. Escherichia coli was identified by MALDI-TOF MS in the feces of 28 of 37 (75.67%) calves, 2 of 3 (66.67%) treated cows, 8 of 14 (57.15%) environmental samples, and the waste milk. Six of 14 (42.85%) environmental samples were also positive for ESBL Acinetobacter baumannii, while all fecal samples were negative. ESBL production was confirmed for all E. coli isolates based on the double disk susceptibility test (DDST), while none were carbapenemase producers. Upon minimal inhibitory concentration (MIC) analysis, all of them showed multiple resistances and were categorized as multi-drug resistant (MDR). This study confirms the widespread presence of MDR, ESBL-E. coli in dairy calves and highlights their diffusion in the farm environment.

Caused by pathogenic microorganisms, such as bacteria, parasites, fungi, among others, infectious diseases can spread directly or from one individual to another. According to the World Health Organization, these diseases are known to cause high mortality rates, severe burdens of disability and serious worldwide aftermaths. The inappropriate use of antibiotics in humans are the main origins of the development of drug-resistant pathogens, which reduce the efficacy of these therapies, thus accentuating the need to search for effective antimicrobials. Medicinal plants have served as starting material for the preparation of a number of antimicrobial agents. To this end, the present study highlights the green synthesis of Cocos nucifera-based nanomaterials and evaluation of the mechanistic basis of their antimicrobial action. Accordingly, Cocos nucifera extract was used to reduce different concentrations (5, 10 and 20 mM) of silver nitrate solution to afford silver nanoparticles (AgNPs). These entities were further incorporated onto activated carbons (obtained by chemical activation using sulphuric acid as activation agent) to generate the nanocomposites. The antimicrobial activity of the as-prepared nanomaterials was evaluated using the broth microdilution method, while, the antioxidant activity was assessed through standard methods, such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Cytotoxicity of potent nanomaterials was assessed on Vero cells by spectrophotometric method. As a result, nanoparticles were successfully synthesized as evidenced by the color change of the solution from transparent to dark brown. Further characterization was carried out by UV-visible spectroscopy that showed an intense absorption spectrum at 433 nm. Fourier Transform Infrared Spectroscopy (FTIR) revealed the functional group moieties involved as a capping and reducing agent in the synthesis of AgNPs. The incubation of nanomaterials with selected bacterial and fungal strains led to significant inhibitory effects of these pathogens with minimum inhibitory concentrations ranging from 7.813 to 250 μg/ml. In antioxidant assays, the nanocomposites presented scavenging activities comparable to that of ascorbic acid. Cytotoxicity experiment revealed no toxic effects on the human mammalian cells Vero (range of selectivity indices: from >4 to >128). These results provide evidence of the implication of Cocos nucifera-based nanomaterials in targeting bacterial or fungal systems that mediate free-radical damage or by inhibiting the oxidative damage caused by selected bacteria and fungi, the most susceptible being Escherichia coli and Candida albicans, respectively.

Salmonella enterica serovar Typhi, is one of the major infection spreading from consuming contaminated food and water. The poor sanitation is one the major cause for successful infection. S. typhi is responsible for causing typhoid fever, which is a growing public health concern in developing countries. This bacterium has acquired antimicrobial resistance to many promising which is a growing health concern for community. This study is aim to elucidate the molecular complexity of flouroquinolone resistance in S. Typhi isolates (n=286). Genomic data was downloaded from NCBI and analysis was done by Resfinder, MLST, and Pointfinder. Genomic analysis unveils a complex resistance profile, featuring antimicrobial resistance genes (ARG) including blaCTXM-15, blaTEM-1D, catA1, dfrA7, qnrS1, sul1, sul2, and tetA(B). The investigation focuses on mutations in DNA gyrA, parC, and qnrS1 genes which plays an important role in quinolone resistance. Mutation analysis reveals mutations such as DNA gyrA_S83F, DNA gyrA_D87N, DNA gyrA_S83Y, DNA gyrB_S464F, parC_S80I, and parE_L416F with the presence of qnrS1 gene produces resistance against quinolones. The Docking studies was conducted by “Autodock vina” and visualize by “Discovery studio” which demonstrate that these mutations leads to ciprofloxacin resistance, indicating reduced binding affinity, and altered solvent accessibility which indicates the structural changes at mutation sites. This study provides crucial insights into the molecular mechanisms driving flouroquinolone resistance in S. typhi, guiding future strategies to combat antibiotic resistance. Further validation through experimental mutagenesis is recommended, for targeted therapeutic interventions against the mounting threat of antibiotic-resistant S. typhi.

Breast cancer is the most common cancer in women globally, often necessitating mastectomy and subsequent breast reconstruction. Silicone mammary implants (SMIs) play a pivotal role in breast reconstruction, yet their interaction with the host immune system and microbiome remains poorly understood. This study investigates the impact of SMI surface topography on host antimicrobial responses, wound proteome dynamics, and microbial colonization. Biological samples were col-lected from ten human patients undergoing breast reconstruction with SMIs. Mass spectrometry profiles were analyzed for acute and chronic wound proteomes, revealing a nuanced interplay between topography and antimicrobial respondseproteins. 16S rRNA sequencing assessed mi-crobiome dynamics, unveiling topography-specific variations in microbial composition. Surface topography alterations influenced wound proteome composition. Microbiome analysis revealed heightened diversity around rougher SMIs, emphasizing topography-dependent microbial inva-sion. In vitro experiments confirmed staphylococcal adhesion, growth, and biofilm formation on SMI surfaces, with increased texture correlating positively with bacterial colonization. This comprehensive investigation highlights the intricate interplay between SMI topography, wound proteome dynamics, and microbial transmission. The findings contribute to understanding host-microbe interactions on SMI surfaces, essential for optimizing clinical applications and minimizing complications in breast reconstruction.

The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing some antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrating remarkable efficacy against planktonic cells and biofilms of MRSA, outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, was showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wound in mice. Together the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.

The fusion of penetrating peptides (PPs), e.g., cell penetration peptides (CPPs), or antimicrobial peptides (AMPs) together with antimicrobial agents is an expanding research field. Specific AMPs, such as lactoferricin B (LfcinB), have demonstrated strong antibacterial, antifungal, and antiparasitic activity, as well as valuable anticancer activity, proving beneficial in the development of anticancer conjugates. The resulting conjugates offer potential dual functionality, acting as both an anticancer and an antimicrobial agent. This is especially necessary in cancer treatment where microbial infections pose a critical risk. Leukemic cells frequently exhibit altered outer lipid membranes compared to healthy cells, making them more sensitive to compounds that interfere with their membrane. In this communication, we revisited and reanalyzed our earlier research on LfcinB and its conjugates. Furthermore, we carried out new experiments with a specific focus on cell proliferation, changes in membrane asymmetric phosphatidylserine location, intracellular reactive oxygen species (ROS) generation, mitochondrial functions, and in vitro bacterial topoisomerase inhibition.

Biofilm-associated bacterial infections are the major reason for treatment failure in many diseases including burn trauma infections. Uncontrolled inflammation induced by bacteria leads to materiality, tissue damage and chronic diseases. Specialized proresolving mediators (SPMs), including maresin-like lipid mediators (MarLs), are enzymatically biosynthesized from omega-3 essential long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (DHA) by macrophages and other leukocytes. SPMs exhibit strong inflammation-resolving activities, especially inflammation provoked by bacterial infection. In this study, we explored the potential direct inhibitory activities of three MarLs on gram-positive (Staphylococcus aureus) and gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria in their biofilms that are leading bacteria in burn trauma related infections. We also examined the effects of MarLs on the bactericidal activities of a typical broad-spectrum antibiotics carbenicillin on these bacteria in their preformed biofilms. The results revealed that MarLs combined with carbenicillin can inhibit the survival of gram-positive and gram-negative bacteria in their biofilms although MarLs alone did not exhibit bactericidal activity. Thus, our findings suggest that the combination of MarLs and carbenicillin can lower the antibiotic requirements to kill the bacteria in preformed biofilms.

In our previous studies, the marine-derived fungus Emericellopsis maritima BC17 was found to produce new eremophilane-type sesquiterpenoids on solid media. In order to explore its potential to produce more metabolites, E. maritima BC17 was subjected to a one strain-many compounds (OSMAC) analysis leading to the discovery of three new eremophilanes (1-3) and fourteen known derivatives (4-17) in the liquid media Czapek Dox and PDB. Their structures were established by extensive analyses of the 1D and 2D NMR, and HRESIMS data, as well as ECD data for the assignment of their absolute configurations. Antitumoral and antimicrobial activities of the isolated metabolites 1, 3, 11, and 15 were investigated. PR toxin 3-deacetyl (15) exhibited cytotoxic activity against HepG2, MCF-7, A549, A2058 and Mia PaCa-2 human cancer cell lines with IC₅₀ values ranging from 2.5 to 14.7 µM. In addition, 15 exhibited selective activity against methicillin-sensitive S. aureus ATCC29213 at the highest concentration tested of 128 µg/mL.

The numerous biological activities of phenothiazine and sulphonamide derivatives, especially their antibacterial qualities, have attracted so much interest. In this study, the synthesis and characterization of phenothiazine-3-sulphonamide derivatives and evaluation their antimicrobial activity against the following pathogenic microorganisms is reported. Two gram-positive bacteria; (Staphylococcus aureus, and Streptococcus pyogenes), two gram-negative bacteria; (Escherichia coli, and Salmonella typhi) as well as one fungus (Aspergillus fumigatus) were used while ciprofloxacin, gentamycin and ketoconazole served as standard drugs. The synthesis of the derivatives was achieved through a base catalyzed the reaction of 4-chloroaniline with 1-naphthylamine to form 1-(naphthalen-1-yl) benzene-1,4-diamine. This intermediate was then treated with sulphur and iodine to yield the phenothiazine derivative while subsequent treatment of the phenothiazine compound with sulphonyl chlorides gave the final products. The synthesized compounds were characterized via proton nuclear magnetic resonance (1HNMR), carbon-13 nuclear magnetic resonance (13C NMR) and Fourier-transform infrared (FTIR) spectroscopic techniques. The minimum inhibitory concentration (MIC) of each compound was then determined using the agar well diffusion method. To predict the binding energies and patterns of the synthesized compounds with target proteins of the above mentioned microorganisms, molecular docking simulations were run using Autodock Vina software (version 4.2). The spectra data of the compounds for FTIR, 1H NMR and 13C NMR (δ) spectral data were consistent with the assigned structures of the synthesized compounds. The binding energies (kcal/mol) for in silico antimicrobial studies were in the range -5.1 to -7.6 kcal/mol. The MIC values were in the range -3.5 to 1.0 mg/L. The results of the in vitro test revealed that the synthesized compounds exhibits promising antimicrobial activity, and showed excellent bactericidal and fungicidal activities. The results obtained showed that the synthesized compounds possess drug-like properties and are good starting materials for drug production.

Background: Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, reduce antimicrobials adverse events as well as control challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple implementation measures. A review of systematic review was conducted to evaluate ASPs process and outcome measures. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary healthcare were evaluated over the past 10 years by examining major and primary databases involving all age groups. Out of 265 identified SR studies, 63 met inclusion criteria, the majority were conducted in European and North American regions. All age groups were examined in the studies but mainly conducted in adults when compared to children and infants . Both ASPs process and outcomes measures were examined equally and simultaneously through 25 different concepts, dominated by efficacy , antimicrobial resistance , and economic impact while information technology as well as role of pharmacy and behavioural factors were equally examined . The main broad conclusions from the review , that across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency while focused evaluation advocate that developed countries should target medium and small sized hospitals while developing countries should continue rolling ASPs in their healthcare facilities . Additionally , the future of ASPs should focus on embracing evolving information technology to bridge gaps in knowledge, alter attitude and enhance decision making .

Bacteria of the genus Staphylococcus are a significant a challenge for medicine, as many species are resistant to multiple antibiotics and even to all of the antibiotics used. One of the approaches to develop new therapeutics to treat staphylococcal infections is the use of bacteriophages specif-ic to these bacteria or lysins of such bacteriophages capable to hydrolyze the cell walls of these bacteria. In this study, a new bacteriophage St_134 specific to Staphylococcus epedermidis was de-scribed. This small podophage belonging to the Andhravirus genus showed relatively wide host range and was able to infect more than 60 strain of Staphylococcus spp., including a clinical strain from the Staphylococcus aureus complex. Two genes encoding different phage lysins were identi-fied in the Ste134 genome. Both lysins LysSte134_1 and LysSte134_2 were produced in Escherichia coli cells. Endolysin LysSte134_1 was demonstrated catalytic activity against a wide panel of staphylococcal peptidoglycans (4 species, 6 strains), was active against S. aureus and S. epidermidis planktonic cultures and destroyed biofilms formed by clinical strains of S. aureus and S. epider-midis.

Fungi of the genus Penicillium produce secondary metabolites used as a model for the synthesis and development of several compounds with bactericidal, fungicidal, antitumor, anti-inflammatory, antiviral activities, among others. Based on this information, a study was conducted to investigate the metabolomic profile and antimicrobial potential of Penicillium purpurogenum (CFAM – 214). The minimum inhibitory concentration (MIC) of extracts obtained from P. purpurogenum broth (CFAM - 214) in ISP2, SB, and YES against Candida albicans was 500 µg/mL, 31.25 µg/mL and 62, 5µg/mL, respectively. In the test against Candida tropicalis and Staphylococcus aureus, the MIC for extracts cultivated in SB was 250 µg/mL and 125 µg/mL, respectively. Due to the good performance of the P. purpurogenum extract in SB, large-scale cultivation was carried out that led to the isolation of two compounds, whose structures were determined by spectroscopic methods such as 1D NMR (1H NMR and 13C NMR) and 2D (HMBC and HSQC), HRMS and MS/MS. The isolated compounds were identified as two citrinin derivatives, dihydrocitrinin (1) and 1-methyl-dihydro citrinin (2).

In recent years, Additive Manufacturing (AM), commonly referred to as 3D printing, has garnered the attention of the scientific community due to its capacity to transform ordinary and traditional items into customized materials at an affordable cost, through various AM processes. Antimicrobial/antibiofilm 3D printed materials are one of the most trending research topics, owing to the growing concerns over the emergence of complex microbial structures called "biofilms" on various surfaces. The review provides an overview of the evolution of additive manufacturing (AM) technologies and their various derivatives, along with a brief description of their materials and applications. It also introduces how biofilms can represent an advantageous lifestyle for microbial populations. The primary objective of this research was to conduct a systematic review on the development of planctonic or biofilm forms of microorganisms on 3D printed materials. The article summarizes commonly studied microorganisms on these materials and presents their 3D printing process, materials, as well as the fields covered by each of the analyzed papers. To the best of our knowledge, this is the first all-inclusive systematic review that amalgamated research conducted in diverse fields to assess the development of biofilms on surfaces produced through three-dimensional printing. Most notably, this review presents a comprehensive account of sustainable approaches for producing antimicrobial materials through 3D printing. Additionally, we assess their advancements in various fields such as medicine, environment, agri-food, and other relevant sectors. The findings of our literature review can be used to recommend appropriate microorganisms, 3D printing materials, and technologies for academic and industrial research purposes focusing on the development of microbial biofilms on 3D printed surfaces. Furthermore, it highlights the potential of environmentally-friendly modified AM technologies to combat biofilms in clinical and non-clinical areas. Our goal with this review is to help readers gain a better understanding of fundamental concepts, inspire new researchers, and provide valuable insights for future empirical studies focused on eradicating biofilms from 3D printed materials.

Acne vulgaris is a prevalent dermatological disorder that impacts the quality of life for millions of people around the world. The multifactorial nature of this disorder requires innovative and effective treatment strategies. Over time, there has been a growing interest regarding the use of natural topical therapies, with cannabinoids emerging as a promising group of compounds for investiga-tion. In the context of acne treatment, cannabinoids are of particular interest due to their anti-acne properties, namely, lipostatic, anti-inflammatory, antiproliferative, and antimicrobial activities. Among these bioactive compounds, cannabidiol stands out as a notable derivative, exhibiting a promising spectrum of therapeutic actions. Pre-clinical and clinical studies have proven its ability to modulate sebum production, reduce inflammation, and inhibit bacterial proliferation - all of which are critical components in the pathogenesis of this dermatosis. This review provides a comprehen-sive overview of cannabinoids' potential as a novel and holistic approach to acne vulgaris treatment and summarizes recent developments in this area.

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Introduction Our aim was to determine the impact of antimicrobial stewardship tools (AST) and COVID-19 pandemic on antibiotic consumption (AC). Methods We used the national software Consores to determine AC in DDD / 1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The AST considered were 1/ internal guidelines 2/ list of antibiotics with restricted access 3/ presence of an antibiotic referent or 4/ an ID specialist 5/ proof of annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. Results In 30 institutions total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin / clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025) respectively, but consumption of piperacillin / tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤ 2 AST had lower AC compared to 20 institutions with ≥ 3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin / tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Conclusion Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC but special attention should be paid on piperacillin / tazobactam consumption.

Diarrhea-related mortality remains an important public health concern, particularly in developing countries, and has become difficult to treat because of antibacterial resistance. The development of synergistic antimicrobial agents appears to be a promising alternative treatment against diar-rheal infections. In this study, the combined effect of tetracycline together with either nitroxoline, sanguinarine, or zinc pyrithione (representing various classes of alkaloid-related compounds) was evaluated in vitro against selected diarrheagenic bacteria (Enterococcus faecalis, Escherichia coli, Listeria monocytogenes, Shigella flexneri, Vibrio parahaemolyticus, and Yersinia enterocolitica). The chequerboard method in 96-well microtiter plates was used to determine the sum of the fractional inhibitory concentration indices (FICIs). Three independent experiments were performed per combination, each in triplicate. It was observed that the combinations of tetracycline with either nitroxoline, sanguinarine, or zinc pyrithione produced synergistic effects against most of the pathogenic bacteria tested, with FICI values ranging from 0.086 to 0.5. Tetracycline-nitroxoline combinations produced the greatest synergistic action against S. flexneri at a FICI value of 0.086. Combinations of the agents tested in this study can thus be used for the development of new anti-diarrheal medications. However, studies focusing on their in vivo anti-diarrheal activity and safety are required before any consideration for utilization in human medicine.

Antibiotic resistance currently considered as a global concern mostly impacting low- and middle-income nations and it can be accelerated by antibiotic abuse and other forms of excessive antibiotic use. There is little data on community practices and understanding in Somaliland on antibiotics and antibiotic resistance. To provide evidence-based communication intervention techniques for safer antibiotic use the qualitative study was done from November 1st to December 1st, 2023, and consisted of in-depth semi-structured interviews with adult heads of households in Hargeisa, Somaliland, using purposive and snowball sampling strategies. Participants were chosen from a variety of medical and educational backgrounds. Thematic analysis was used to investigate community knowledge and antibiotic use in the sampled population. To investigate the level of awareness on antibiotic use, 20 respondents (households) were questioned (Table 1). Of these, 17 (85%) became aware of the term antibiotic itself, with 7 (35%) being prescribed by a physician, 9 (45%) receiving laboratory diagnosis when using antibiotics, and 6 (30%) becoming aware of the potential risks associated with improper antibiotic use. This study highlighted the community's lack of understanding about antibiotic use. The majority of the study participants knew the phrase "antibiotic" but had no idea what it meant, the side effect of the antibiotics and other medical science related information regarding how to safely use antibiotics. According to the findings, initiatives for antibiotic stewardship should focus on community education to prevent antibiotic misuse or abuse.

Recent evidence suggests that the lower gut microbiome of ruminants presents roles in their health and environment, including the development of the mucosal immune system, milk production efficiency and quality and subsequent methane emissions. However, there are proportionately fewer studies on this complex microbial community in cattle and region-focus studies are non- existent. Herein, we present the research protocol of the GUTBIOME CY project pertaining to determine the composition of the lower gut microbiome in dairy cows situated in 37 farms across five districts of the island of Cyprus. Detailed questionnaires on animal husbandry and farming practices will be gathered from each farm. Faecal, milk (individual and bulk) and water samples will also be collected from cows and their offspring. Samples will be analysed using a combination of molecular biology and bioinformatics pipelines to define microbiome profiles and antimicrobial resistance (AMR). Information collected from the questionnaires will be use to test for associations between animal husbandry or farming practices and microbiome components and AMR. Collected samples will establish the first dairy cattle biobank in the country for contributing substantially towards scientific advancements in microbiome research and providing insights to all stakeholders, tailored to the unique agricultural context of Cyprus.

Background : Probiotics are composed of microorganisms that have positive effects on health when consumed in prescribed quantities. Lately, studies have attempted to establish this role of probiotics in enhancing health. Aim : The aim of this study was to compare the antifungal activity of 3 different probiotics against Candida albicans.Methodology :This was an in-vitro study. 3 types of commercially available probiotics - Bifilac, Pre pro HS and VSL-3 were cultured separately with Candida albicans and were placed under incubation. The maximum zone of inhibition was recorded for each of the probiotic solutions.Results : In this study, it was found that among the three probiotic products, Bifilac exhibited a maximum zone of inhibition of 13mm at concentration of 100µL against C. albicans, while Pre pro HS and VSL-3 showed zone of inhibition of 11mm at concentrations of 50µL and 100µL, respectively.Conclusion : Within the limits of the present study, This study could prove that probiotics can be considered as an alternative and safe treatment option for treatment of Oral candidiasis infections.

Surgical site infections (SSI) occur very frequently during post-operatory procedures and are often treated with oral antibiotics, which may cause some side-effects. This type of infections could be avoided by encapsulating antimicrobial/anti-inflammatory drugs within the surgical suture materials so that these can more efficiently act on the site of action during wound closure, avoiding post-operatory bacterial infection and spreading. This work was aimed at developing novel electrospun biobased anti-infective fiber-based yarns as novel suture materials for preventing surgical site infections. For this, yarns based on flying intertwined nanofibers were fabricated in-situ during the electrospinning process using a specially designed yarn collector. The electrospun yarn sutures were made of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) with different contents of 3HV units and contained ciprofloxacin hydrochloride (CPX) as the antimicrobial active pharmaceutical ingredient (API). The yarns were then analyzed by scanning electron microscopy, Fourier transform infrared spectroscopy, wide-angle X-ray scattering, differential scanning calorimetry and in vitro drug release. The yarns were also analyzed in terms of antimicrobial and mechanical properties. The material characterization indicated that the varying polymer molecular architecture affected the attained polymer crystallinity, which was correlated with the different drug-eluting profiles. Moreover, the materials exhibited the inherent stiff behavior of PHBV, which was further enhanced by the API. Lastly, all the yarn sutures presented antimicrobial properties for a time release of 5 days against both gram positive and gram-negative pathogenic bacteria. The results presented highlight the potential of the herein developed antimicrobial electrospun fiber yarns as potential innovative suture materials to prevent surgical infections.

Metformin is an oral antidiabetic agent with antimicrobial properties, excreted in an active and unmetabolized form. Like some non-antibiotic drugs, subinhibitory concentrations of metformin may contribute to the expression of microbial resistance in wild-type strains. This work aimed to evaluate the biofilm formation of Pseudomonas aeruginosa TGC04 exposed to 100 and 200 µg/mL of metformin, varying the Chemical Oxygen Demand (COD) and flow regime. Biofilms were quantified after 2 and 24 hours, observing reductions and increases in biofilm growth around 13 and 64%, respectively. The greatest biofilm growth occurred in cells exposed to 200 µg/mL of metformin. Both the flow regime and COD concentration were important for the development of the biofilm, whose cells were mostly weakly to moderately adhered. The study provides evidence that in polluted aquatic systems with turbulent regimes, the inhibitory concentration of metformin promoted the least disturbances to the biofilm.

Organometallic drug development is still in its early stage, but recent studies show that organometallics having iron as the central atom have the possibility of becoming good drug candidates because iron is an important micro-nutrient, and it is compatible with many biological systems, including the human body. Being an eco-friendly Lewis acid, iron can accept the lone pair of electrons from imino(sp2)-nitrogen, and the resultant iron-imine complexes with iron as a central atom have the possibility of interacting with several proteins and enzymes in humans. Iron-imine complexes have demonstrated significant potential as anticancer, bactericidal, fungicidal, and other medicinal activities in recent years. This article systematically discusses major synthetic methods and pharmacological potentials of iron-imine complexes having in vitro activity to significantly affect clinical performance from 2016 to date. In a nutshell, this manuscript offers a simplistic view of iron complexes in medicinal inorganic chemistry: for instance, iron is presented as an "eco-friendly non-toxic" metal (as opposed to platinum) that will lead to non-toxic pharmaceuticals. The abundant literature on iron chelators shows that many iron complexes, particularly if redox-active in cells, can be quite cytotoxic, which can be beneficial for future targeted therapies. While we made every effort to include all the related papers, any omission is purely unintentional.

Abstract: One of the most significant medical advancements of the 20th century was the discovery of antibiotics, which continue to play a vital tool in the treatment and prevention of diseases in humans and animals. However, the imprudent use of antibiotics in all fields of One-Health and concerns about antibiotic resistance among bacterial pathogens have raised interest in antibiotic use restrictions on a global scale. Despite the failure of conventional antimicrobial agents, only about 15 new antibiotics have been introduced clinically since year 2000 to date. Moreover, there have been reports of resistance to some of these new antibiotics. This has necessitated a need to search for an alternative strategy to combat antimicrobial resistant pathogens. Thus, this review compiles and evaluates the approaches—natural compounds, phage treatment, and nanomaterials—that are being used and/or suggested as the potential substitutes for conventional antibiotics. These strategies include those that focus on the enzymes or proteins, as well as the physiology and metabolism of resistant bacteria

Due to their wide range of uses in modern technology, nanomaterial’s of silver metallic (Ag-NPs) have engaged considerable concern, driving significant research with development efforts. This study focuses on investigating the antimicrobial properties of Ag-NPs, encompassing their production, characterization, and biological aspects. The eco-friendly extracellular biosynthetic method employed in this work utilized extracts from the marine fungus Aspergillus flavus MK4 as reducing agents for nanoparticle synthesis. Analyzing the colloidal Ag-NPs using UV-visible spectroscopy revealed a peak in absorbance at 460 nm, indicating the presence of plasmonic properties. The electrons imaging of internal structure (TEM) elucidated spherical shape of the Ag-NPs by 15 nm size. Testing against bacterial diversities (Gr-ve & Gr+ve) revealed potent antibacterial and antifungal efficacy. Cytotoxicity versus HepG-2 cell line was assessed using the MTT assay, and antioxidant properties were examined through the radical scavenging (DPPH) assay. In wise of their conceivable applications in the fields of antibacterial, anticancer, and wound-healing, the Ag-NPs that were synthesized exhibit promising features. With its powerful ability to synthesize silver nanoparticles (Ag-NP), Aspergillus flavus MK4 Aspergillus flavus MK4 can generate nanoparticles extensively characterized, demonstrating their antibacterial, antioxidant, anticancer, and wound-healing properties.

Schinus terebinthifolius Raddi is a plant native to Brazil. The objective of this work was to analyze the chemical composition, antioxidant and antibacterial potential of essential oils (EOs) from the leaves, fruits and twigs of S. terebinthifolius aiming for their application in food safety. EOs were obtained by hydrodistillation and the chemical composition was determined by gas chromatog-raphy coupled to mass spectrometry. Phenolic compounds were quantified and antioxidant ac-tivity was evaluated using three different methods. The antibacterial activity was determined by the broth microdilution method against foodborne bacteria. In the chemical analysis, 22 com-pounds were identified in the leaves, 13 compounds in the fruits and 37 compounds in the twigs, revealing the presence of the main compounds germacrene D, caryophyllene, α-pinene, β-pinene and γ-gurjunene. EOs showed better antioxidant potential using the β-carotene/linoleic acid method with 40.74, 61.52 and 63.65% oxidation inhibition for leaves, fruits and twigs, respectively. The EO from the leaves showed greater antibacterial potential against Escherichia coli and Staphy-lococcus aureus with a minimum inhibitory concentration (MIC) of 0.62 mg mL-1, values lower than the MIC of sodium nitrite (5.00 mg mL-1), antimicrobial standard synthetic. The activities of pink pepper EOs suggest their potential as a biopreservative in foods.

The study aims to evaluate the Quorum Sensing (QS) system inhibition against some Gram-positive and Gram-negative bacteria detected by molecular modeling of R. cathartica L. plant extract. R. cathartica L. methanol extract was evaluated in vitro. The research was carried out for the possible role and mechanism of R. cathartica L. The antibacterial activity of R. cathartica L. seed extract on some Gram-positive and Gram-negative strains was evaluated using culture-based and computational analysis. Gentamicin (CN; 30 µg/ml, Bioanalyse) was used as an antibacterial control of the extract on the production potential of QS-dependent virulence factors on Pseudomonas aeruginosa PAO1 was investigated. Phytochemical analysis resulted in the identification of 23 phenolic phytochemicals. R. cathartica L. extract was observed to have antimicrobial activity against Gram-positive and Gram-negative bacteria at different rates (11.3 mm-16 mm). The inhibitory effect of R. cathartica L. extract on P. aeruginosa PAO1 (elastase 61%, pyocyanin 18%, and biofilm 61%) was recorded moderately. Phytochemical analysis revealed that the main component of the extract is kaempferol. Therefore, the binding potential of kaempferol on QS system receptors was investigated via molecular docking. Computational analysis showed that kaempferol can inhibit the QS system by preventing competitive ligands from connecting to LasR. This study explored the activity and mechanism of action for a new green alternative against resistance. might provide a mechanism for R. cathartica L. seed extract components and thus provide a new avenue for using R. cathartica L. seed extract as a green antibacterial agent.

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain com-pounds with fewer side effects, at the same time effectively overcoming the problem of antimi-crobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important sup-port for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of FT-ICR and LTQ mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribu-tion and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

Single-fluid electrospinning creates nanofibers from molten polymer solutions with active ingredients. The study utilized a combination of a fractional factorial design and a Box-Behnken design to examine crucial factors among a multitude of parameters and to optimize the electrospinning conditions that impact the fiber mats' morphology and entrapment efficiency of the Senna alata leaf extract. The findings indicated that the shellac content had the greatest impact on both fiber diameter and bead formation. The optimum electrospinning conditions were identified as a voltage of 24 kV, a solution feed rate of 0.8 mL/h, and a shellac-extract ratio of 38.5:3.8. These conditions produced nanosized fibers with a diameter of 306 nm, a low bead-to-fiber ratio of 0.29, and an extract entrapment efficiency of 96% within the fibers. The biphasic profile of optimized nanofibers was confirmed through an in vitro release study. This profile consisted of an initial burst release of 88% within the first hour, which was succeeded by a sustained release pattern surpassing 90% for the next 12 h, as predicted by zero-order release kinetics. The optimized nanofibers demonstrated antimicrobial efficacy against diverse pathogens, suggesting promising applications in wound dressings and protective textiles.

Globally, the use of whole-cell matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) in clinical microbiology laboratories has increased considerably. With the rapid growth of artificial intelligence technology, there is an increasing number of areas devoted to solving problems by implementing machine learning-based methods. Applying the use of artificial intelligence to the analysis of the massive amount of information obtained in the mass spectrum derived from MALDI-TOF MS should be a breakthrough in clinical microbiology. Specifically, it would facilitate a more rapid and accurate strain typing or antibiotic susceptibility test (AST) based on whole-cell MALDI-TOF MS spectra, and hence, it is a promising solution. Even though the reproducibility of peaks could result in some critical problems, computational methods have been developed to address this issue. Therefore, clinical microbiologists are able to perform strain typing or an AST as smoothly and easily as identifying species by using MALDI-TOF MS and artificial intelligence.

The ESKAPE pathogens are public health concerns worldwide, defining the present major antibiotic resistance issues: E. faecium vancomycin-R, S. aureus methicillin-R, Ps. Aeruginosa and A. baumannii carbapenem-R, resistance to 3rd generation cephalosporins of Kl. pneumoniae and Enterobacter spp. Covid-19 pandemic disturbed the health care usual procedures, contributing to the spread of antibiotic-resistant bacteria. The present study retrospectively assessed the prevalence and antimicrobial resistance (AMR) profile of ESKAPE microorganisms during 2020-2022 in a multidisciplinary emergency hospital from Romania, based on microbiological reports. The AMR issues mainly interest the urology department. ESKAPE group accounts for 33.5% of the total bacterial isolated. The specific AMR of ESKAPE pathogens cumulates 30.9%, while antimicrobial multidrug resistance characterizes 21% from all ESKAPE strains. Kl. Pneumoniae, followed by S. aureus, and Ps. aeruginosa are the main hospital problems concerning the ESKAPE surveillance. The directions of the near future antibiotic stewardship program focus to revise the clinical protocols for diagnostic and treatment in each department, to intensify the bacteriological samples collection, to improve the microbiological diagnostic techniques for AMR identification, to continue the epidemiological current actions of surveillance, control, and education.

Drug-resistance represents one of the great plagues of our time worldwide, largely limiting the treatment of common infections, and accounting for the urge in the development of new antibiotics or other alternative approaches. Noteworthy, the indiscriminate use of antibiotics is mostly responsible for the selection of mutations that confer drug-resistance to microbes. Recently, beyond molecules of natural origin and synthetic ones studied to tackle microbial infections, ozone is raising interest for its unique biological properties, in particular when dissolved in natural oils. In fact, ozonated oils have been reported to act in a non-specific way on microorganisms hindering the acquisition of advantageous mutations resulting in resistance. Here, we focused on comparing the antimicrobial effect of two different types of ozonated oils over a panel of opportunistic and pathogenic microbes. Ozonated olive (OOO) and sunflower seeds (OSO) oils were preliminarily characterized by chemico-physical investigation and tested by in-vitro experiments. Candida albicans, Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Escherichia coli have been challenged with different ozonated oils concentrations to evaluate their antimicrobial profile by agar diffusion and broth dilution methods. Cytotoxicity was also evaluated in keratinocytes and endothelial cells. Overall, our results revealed that both OOO and OSO showed a potent microbicidal effect especially against C. albicans (IC50 = OOO: 0.3 mg/mL and OSO: 0.2 mg/mL) and E. faecalis (IC50 = OOO: 0.4 mg/mL and OSO: 2.8 mg/mL) albeit exerting a certain effect also against S. aureus and E. coli. Moreover, both OOO and OSO do not yield any relevant cytotoxic effect at the active concentrations in both cell lines indicating that these ozonated oils are not toxic for mammalian cells despite exerting a potent antimicrobial effect on specific microorganisms. Therefore, OOO and OSO may be considered to integrate standard therapies in the treatment of common infections, likely overcoming drug resistance issues.

Antimicrobial resistance (AMR) is a growing public health issue worldwide that affects the world economy. The concern associated with this issue increased during the COVID-19 pandemic. The misuse of antibiotics during the COVID-19 pandemic will have catastrophic implications for the control of AMR. In 2019, the coronavirus illness COVID-19 first appeared in China. COVID-19 infection is a surface-to-surface communicable disease. It is considered the most vital global health disaster of the century. It has rapidly spread around the world and is the greatest challenge for humankind. This chapter discusses the origin, symptoms, transmission, treatment, and recommendations of the COVID-19 disease.

One of the main families of antimicrobial peptides (AMPs) derived from the skin secretions of Hylidae frogs are dermaseptins. Among them, dermaseptin S4 (DS4) is characterized by its broad spectrum of activity against bacteria, protozoa and fungi. This study determined the physicochemical properties of the native peptide DS4(1-28) and its derivatives [DS4(1-28)a and DS4(1-26)a] isolated from the skin of the frog Phyllomedusa sauvagii and examined their antimicrobial properties against two marine pathogenic bacteria (Vibrio harveyi and V. anguillarum). The results indicate that DS4(1-26)a has high bacteriicdal activity against the tested strains and low hemolytic activity (&gt; 30 % lysis at the highest tested concentration of 100 µg mL-1) compared to the other two peptides. In addition, all three peptides affected the membrane and cell wall integrity of both pathogenic bacteria, causing leakage of cellular contents, with DS4(1-26)a having the most severe impact. These properties were corroborated by tansmission electron microscopy and by the variation of cations in their binding sites due to the effect of AMPs. These results suggest that DS4 and its derivatives, particularly the truncated and amidated peptide DS4(1-26)a, could potentially be effective in the treatment of infections caused by these marine pathogenic bacteria. Future experiments are required to validate the use of DS4 in vivo in the prevention of fish bacterial diseases.

Triphenylphosphonium (TPP) derivatives of a decapeptide related to sequences of bactenecin 7 (Bac7) and oncocin (Onc112) were synthesized and studied as potential antimicrobial compounds using various biochemical and microbiological assays. It was shown that while the reduction of the Bac7 length to 10 a.a. residues dramatically decreases the affinity to bacterial ribosomes, the modification of peptide with alkyl-TPP moieties leads to an increase in the affinity. New analogs which structure combines a decapeptide related to Bac7 and Onc112 — Bac(1-10, R/Y) — and TPP, attached to the C-terminal amino acid residue through alkylamide linkers, inhibit translation in vitro and are found to be more selective inhibitors of bacterial translation as compared with eukaryotic translation, than Onc112 and Bac7. Triphenylphosphonium analogs of a decapeptide related to Bac7 and Onc112 suppress the growth of both gram-negative bacteria, similar to Onc112 and Bac7, and gram-positive ones as alkyl-TPP derivatives, and also act against some resistant laboratory strains. Bac(1-10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, is transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1-10, R/Y) containing either decylamide or ethylamide linker cause B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1-10, R/Y)-C2-TPP analog is proved to be non-toxic for mammalian cells by MTT-test.

Antimicrobial resistance is one of the most important global health issues identified in recent decades. Different approaches have been used to establish the presence and abundance of antimicrobial resistance genes (ARGs) in the environment. In this study, we analyzed soil samples from Fildes Peninsula (King George Island, maritime Antarctica), exposed to different types of impact. The objective of the work was to identify ARGs in the samples, and evaluate if these genes were located in plasmids, using two different strategies. A metagenomic analysis was used to identify ARGs and if they were associated to plasmid sequences. The analysis showed that the site highly exposed to anthropogenic activity had a higher number of ARGs compared to other sites. A high percentage of those ARGs (19.4%), were located in plasmidic contigs. We also assessed replicon mobilization, using microbial communities from these soil samples as donors through an exogenous plasmid isolation method. In this case, we could recover plasmids with ARGs in a Tcr transconjugant clone. Although they could not be fully assembled, we could detect broad host range IncP1 and IncQ plasmid sequences. Our results indicate that sewage impacted soils could be a hotspot for ARGs spread into the Antarctic environment

Indigo leaves form various plant species are sources of dyes/pigments, not fully exploited for making sustainable textiles. Blue indigo vat dye extracted from indigo leaves, yields high wash colorfastness but fades slowly with light, and is not easily used for direct printing. Indigo leaves can be used to produce textiles of various color shades, while light resistant Mayan-inspired hybrid pigments have not yet been used for textile coloring. Using blue indigo dyes from 3 plant species, with exhaustion dyeing, intense wash resistant blue colored textiles are produced, and in the case of Indigofera Persicaria tinctoria, textiles have antibacterial activity against S. Epidermis and E. Coli.100% Natural Mayan-inspired blue indigo pigment, made from Sepiolite clay and indigo dye, was used both in powdered and paste forms to perform pigment textile dyeing by pad cure process, and direct screen printing on textiles. A water-based bio-binder (40%) was used efficiently for both padding and printing. Bio-based Na Alginate thickener allowed color fast printing on both polyester and cotton fabrics, while bio-based glycerin allowed good print color fastness on polyester only, yielding prints with excellent color fastness to wash (5/5), to dry and wet rubbing (5/5) and light (7/7).

Antimicrobial peptides (AMPs) are essential components of the innate immune system, present across a spectrum of organisms. Their versatility lies in their ability to effectively inhibit a wide range of pathogens including bacteria, fungi, parasites, and viruses. As the challenge of antibiotic resistance escalates and concerns surrounding antibiotic use grow, AMPs have emerged as promising alternatives. Their applications span diverse domains such as medicine, agriculture, food production, animal husbandry, and aquaculture, primarily due to their efficacy against resistant pathogens, signifying their crucial role in combating infections. Beyond their antimicrobial properties, research illuminates their intricate involvement in the immune response network. These peptides impact crucial processes including cytokine release, chemotaxis, wound healing, angiogenesis and the activation of the adaptive immune system. This comprehensive review delves into the multifaceted realm of AMPs, encompassing their classification, varied applications across industries and notably, their significance in diverse disease conditions like infections, skin diseases, cancer, oral diseases, lung diseases and cardiovascular ailments. Special attention is directed towards current advancements in clinical applications of peptide-based therapeutics, offering invaluable insights into their potential future integration within clinical settings.

Delivery systems of the biologically active substance such as proanthocyanidins (PCAN) produced through the electrospinning method were designed using a blend of poly(L-lactide-co-glycolide) and poly[(R,S)-3-hydroxybutyrate]. The research involved the structural and thermal characteristics of the developed electrospun three-dimensional fiber matrix, as well as hydrolytic degradation tests performed on them. Additionally, the release profile of PCAN from the electrospun nonwoven was determined using UV–VIS spectroscopy. Approximately 30% of PCAN was released from the tested electrospun nonwoven during the initial 15-20 days of incubation. The chemical structure of water-soluble oligomers that were formed after the hydrolytic degradation of the developed delivery system was identified through electrospray ionization mass spectrometry. Oligomers of lactic acid and OLAGA oligocopolyester, as well as oligo-3-hydroxybutyrate terminated with hydroxyl and carboxyl end groups, were recognized as degradation products released into the water during the incubation time. It was also demonstrated that variations in the degradation rate of individual mat components influenced the degradation pattern, and the number of formed oligomers. The obtained results suggest that the incorporation of proanthocyanidins into the system slowed down the hydrolytic degradation process of the poly(L-lactide-co-glycolide)/poly[(R,S)-3-hydroxybutyrate] three-dimensional fiber matrix. In addition, in vitro cytotoxicity and antimicrobial studies advocate the use of PCAN for biomedical applications with promising antimicrobial activity.

Antimicrobial resistance is an increasing problem for the global public health. One of the strategies to combat this issue is the synthesis of novel antimicrobials through rational drug design based on extensive structure-activity relationship studies. The thiazole nucleus is a prominent feature in the structure of many authorized antimicrobials, being clubbed with different heterocycles. The purpose of this review is to study the structure-activity relationship in antimicrobial thiazoles clubbed with various heterocycles reported in the literature between 2017 and 2022, in order to offer an overview of the last years in terms of antimicrobial research and provide a helpful instrument for future research in the field.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

This paper presents a novel cheminformatics approach for the design and synthesis of hydroxyapatite/collagen nanocomposites, which have potential biomedical applications in tissue engineering, drug delivery, orthopedic and dental implants. The nanocomposites are synthesized by the co-precipitation method with different ratios of hydroxyapatite and collagen, and their mechanical, biological, and degradation properties are analyzed using various experimental and computational techniques, such as attenuated total reflection Fourier-transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, scanning electron microscopy with energy-dispersive X-ray spectroscopy, and molecular simulation. The antimicrobial activity of the nanocomposites is evaluated in vitro against several bacterial and fungal strains, demonstrating their medical potential. Additionally, in silico analyses are performed to predict the absorption, distribution, metabolism, and excretion properties and the bioavailability of the collagen samples. This work opens new avenues for the development of novel biomaterials using cheminformatics tools and methods, which can facilitate the optimization of the design and synthesis parameters, as well as the prediction of the biological outcomes. Future research directions include the investigation of the biocompatibility and bioactivity of the nanocomposites in vivo, as well as the exploration of other applications and functionalities of these nanocomposites.

The accumulation of microorganisms, plants, algae, or small animals on wet surfaces that have a mechanical function causes biofouling, which can result in structural or other functional deficiencies. The maritime shipping industry must constantly manage biofouling to optimize operational performance, which is a common and long-lasting problem. It can occur in any metal structure in contact or submerged in ocean water, which represents additional costs in terms of repairs and maintenance. This study is focused on the production of antifouling coatings, made with nanoparticles of copper selenide (CuSe) modified with gum arabic, within a water-base acrylic polymeric matrix. During the curing of the acrylic resin, the CuSe NPs remain embedded in the resin but this does not prevent the release of ions. The coatings presented to release copper and selenium ions for up to 80 days, selenium was the element that was released the most. The adhesion of film coatings to metallic substrates showed good adhesion, scale 5B (ASTM D3359 standard). Antimicrobial activity tests show that the coatings have an inhibitory effect on Escherichia coli and Candida albicans. The effect being more noticeable when the coating is detached from the substrate and placed on a growing medium, than compared to the coating on a substrate. Scanning electron microscopy (SEM) observations show that nanostructured CuSe coatings are made up of rod-shaped and spherical particles whose range ranges from 12 to 25 nm. The Energy Dispersive X-ray spectroscopy (EDS) studies showed that the ratio of selenium nanoparticles is greater than that of copper and that their distribution is homogeneous

Using qRT-PCR analysis, the LcIL-8 expression level indicated broad expression in most detected tissues, with the most predominant expression in whole blood at 6 to 24 h after infection with S. iniae at concentrations of 105 colony-forming unit (CFU)/fish (p &lt; 0.05). After immersion with F. covae, the LcIL-8 transcript was upregulated in the gills, liver and intestine, with the highest expression level found in the gills. However, LcIL-8 was downregulated in all tested tissues at 48 and 96 h after infection with the two pathogenic strains, indicating that Lc-IL8 has a short half-life during the early immune responses to pathogens. MIC analysis of rLcIL-8 protein against S. iniae was 10.42 ± 3.61 µg/mL. Furthermore, the functional analyses clearly demonstrated that 10 and 100 µg of rLcIL-8 protein efficiently enhanced the phagocytic activity of Asian seabass phagocytes in vitro (p &lt; 0.05). Additionally, in vivo injection of S. iniae following the rLcIL-8 protein indicated that 50 and 100 µg of rLc-IL-8 were highly effective in protecting fish from the tested pathogen (p &lt; 0.001). These results indicate that rLcIL-8 plays a crucial role in the defense mechanisms against bacterial infections in the target fish.

Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a predominant cause of mortality, especially in low- and middle-income nations. Recently antimicrobial peptides were discovered that at low concentrations could stimulate the growth of M. tuberculosis (hormetic response). In this study, such a peptide was used to investigate the effects on the time to positivity (TTP). A systematic substitution analysis of peptide 14D was synthesized using Spot synthesis technology, resulting in 171 novel peptides. Our findings revealed a spectrum of interactions, with some peptides accelerating M. tuberculosis growth, potentially aiding in faster diagnostics, while others exhibited inhibitory effects. Notably, peptide NH2-wkivfiwrr-CONH2 significantly reduced the TTP by 25 hours compared to the wild-type peptide 14D, highlighting its potential in improving TB diagnostics by culture. Several peptides demonstrated potent antimycobacterial activity, with a minimum inhibitory concentration (MIC) of 20 µg/mL against H37Rv and a multidrug-resistant M. tuberculosis strain. Additionally, a reduction in the formation of cord-like structures was observed, which is indicative of reduced virulence and transmission potential. This study underscores the multifaceted roles of antimicrobial peptides in TB management, from enhancing diagnostic efficiency to offering therapeutic avenues against M. tuberculosis.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

Global agriculture has been forced to increase food production to feed the growing human population, while confronting various environmental obstacles such as global warming, resistance to pathogens, and constraints on arable land caused by soil salinity, drought, rising sea level, saltwater intrusion, and urbanization. Regarding abiotic stresses, salinity is a worldwide problem for agricultural production. Many efforts, therefore, have been made to cope with the environmental challenges, however, the progress of salinization, which is mainly caused and accelerated by anthropogenic activities, is likely faster than our progress in finding ways to deal with this problem. In addition, drought represents a global threat to the production of major crops. In addition, pests and pathogens cause significant crop losses and diminish global food security. Among the various strategies that have been investigated and applied in plant science, antimicrobial peptides derived from plants have caught widespread attention from scientists since these peptides exhibit beneficial biological activities. In agricultural science, there have been reports on the roles of antimicrobial peptides with active properties against biotic and abiotic stresses. Non-specific plant lipid transfer proteins, thionins, systemins, defensins, cyclotides, and heveins-like antimicrobial peptides are common antimicrobial peptides that have been found to be involved in the defense system against fungi and insect pests. Based on their potential ability to protect crops from pests, bacteria, and pathogenic fungi, the use of antimicrobial peptide genes in creating transgenic plants has been largely conducted during the last decades, and these studies have obtained positive results against the growth of fungi and bacteria. This review will focus on the latest progress in studies of antimicrobial peptides related to biotic and abiotic stress tolerance in plants. We will also update the current progress in the development of antimicrobial peptide-based transgenic crops.

Cissus populnea Guill. & Perr. (Vitaceae) is used in traditional medicine to treat microbial infec-tions, venereal diseases, and infertility, among others. The aim of the research is to isolate and characterize the antimicrobial constituent(s) from the stem of C. populnea. The n-butanol fraction of C. populnea being most active was subjected to silica gel column chromatography which led to the isolation of a white solid and white crystalline substances coded compounds C1 and C4C5, respectively. Spectral analysis (1D & 2D-NMR) of the isolated compounds and comparison with literature data indicated C1 to be Bis-(2-ethyloctyl)-phthalate and C4C5 to be a mixture of stig-masterol and β-sitosterol; C4C5 exhibited zone of inhibition ranging from 24 – 29 mm against the test organisms with Candida albicans being the most sensitive organism while Trichophyton rubrum was the least sensitive organism. The standard drugs, Ciprofloxacin had 27 – 37 mm while Flu-conazole and Fulcin exhibited zone of inhibition ranging from 34 mm and 29 – 32 mm, respec-tively. The MIC and MBC/MFC values for C4C5 ranges from 12.5 – 25.0 µg/cm3 and 25.0 – 50.0 µg/cm3 against MRSA, S. aureus, E. coli, C. albicans, T. rubrum, and T. mentagrophyte, respectively. In conclusion, three bioactive compounds were identified for the first time from the stem of C. populnea

The wound management sector has attracted considerable attention due to the increasing challenge posed by antimicrobial resistance (AMR) and the specialized care required for chronic wounds. Effective wound care involves selecting appropriate dressings tailored with antimicrobial agents to prevent bacterial infection. Among various types of wound dressings, fibers and electrospun fibers, with their unique characteristics, have emerged as innovative new materials. However, the rise of AMR necessitates the exploration of new antimicrobial agents for wound dressings, particularly for addressing bacterial pathogens like methicillin-resistant Staphylococcus aureus (MRSA). Endophytic fungi, known for producing diverse bioactive compounds, including novel antibacterial agents, represent a promising source of such new agents. This study tested thirty-two endophytic fungi from thirteen distinct Australian native plants for their antibacterial activity against S. aureus, the most common wound-associated bacteria. Ethyl acetate (EtOAc) extracts from fungal culture filtrates exhibited inhibitory effects against both methicillin-sensitive S. aureus ATCC 25923 and MRSA strains M173525 and M180920. DNA sequence analysis was employed for fungal identification, with EtOAc extracts from the most active sample, EL 19 (Chaetomium globosum), selected for further bactericidal and antibiofilm testing against the chosen bacteria. Biofilm of S. aureus ATCC 25923 was reduced by 55% by EtOAc extracts of EL 19 at 1/2 × MIC. To demonstrate the potential application in wound dressing materials, three different concentrations of the extract were incorporated into Polycaprolactone fiber mats through electrospinning, with resultant inhibition of S. aureus ATCC 25923 being observed. This research underscores the potential of endophytic fungi from Australian plants as sources of substances effective against common wound pathogens. Further exploration of the responsible compounds and their mechanisms could facilitate the development of wound dressings effective against MRSA and innovative biofilm-resistant electrospun fibers, contributing to the global efforts to combat AMR.

Staphylococcus aureus(S. aureus) is associated with mastitis in dairy cows, this study investigates the therapeutic effect of maggot antimicrobial peptides on S. aureus induced mastitis in mice. The maggot AMP was isolated and purified, tested for antimicrobial activity, and used to treat a pathological model of rat mastitis. The concentration of 1.5mg/（Kg. BW）AMP was selected as intramammary treatment in S. aureus-induced mastitis in mice. The mice were divided into four groups of 30 mice each: group I (healthy control), group II (disease control), group III (AMP), and group IV (ciprofloxacin). To evaluate the therapeutic efficacy of maggot AMP in mastitis induced by S. aureus based on clinical presentation, mammary gland structure, bacterial load, histopathology, and cure. During the 7-day treatment period, all the mice in Group II died in the afternoon of the fifth day, and the clinical signs of the mice in Group III began to improve on the third day, as evidenced by the gradual recovery of the mice's mental status, dietary intake, and water intake. During the treatment period, the bacterial load count of Group III was significantly lower than that of Group II but higher than that of Group IV, while the bacterial load count of Group III gradually decreased and approached that of Group IV from the fifth to the seventh day. The levels of TNF-α in groups III and IV were significantly lower than those in group II, suggesting that maggot AMP has a certain inhibitory effect on TNF-α. Treatment with AMP@ 1.5 mg/(Kg. BW) showed restoration of clinical signs, reduced bacterial load, and lower TNF-α levels in mice, leading to significant improvement in histopathological changes as compared to disease controls. The final cure rate was 40% for mice in Group III compared to 70% for mice in Group IV, compared to all mice in Group II that died. From this study, it can be concluded that maggot AMP can be used as a potential alternative treatment option to antibiotics for the treatment of bovine mastitis.

In our previous work, we demonstrated the potential of the amphiphilic cyclic peptide [W4R4] as a promising antimicrobial agent. The extensive data accumulated on the antimicrobial activity of this peptide and its homologs presented an opportunity to unravel the molecular mechanisms governing their action and establish crucial structure-activity relationships (SAR). To achieve this, we employed a comprehensive approach involving peptide synthesis, in vitro biological testing, and molecular modeling to systematically analyze the SAR of a series of cyclic peptides derived from the [W4R4] scaffold. Minimal modifications were introduced to the original peptide by incorporating either one aromatic hydrophobic residue (W) or one polar positively charged residue (R) while maintaining the sequential W/R arrangement. Additionally, we introduced an "intermediate" substitution by incorporating 2,5-diketopiperazine (DKP), possessing both aromatic and polar properties, into the macrocycle [W4R4] between the W and R residues. Notably, this study marked the first synthesis and evaluation of the [W4R4(DKP)] peptide. Structural, dynamic, hydrophobic, and membrane-binding properties of four cyclic peptides ([W4R4], [W5R4], [W4R5], [W4R4(DKP)]) were explored using molecular dynamics simulations within a DOPC/DOPG lipid bilayer that mimics the bacterial membrane. The results obtained revealed distinct SAR profiles for all peptides, enabling the establishment of correlations between their antimicrobial activity and structural/dynamic parameters. These parameters included the degree of conformational plasticity, the depth of immersion into the bi-layer, and the population of the membrane binding mode characterized by the embedding of the hydrophobic peptide pattern into the acyl chain region of lipids. In particular, the peptide [W4R5] exhibited an optimal "activity/binding to the bacterial membrane" pattern. This work highlights the significance of our multidisciplinary approach in efficiently deciphering finely regulated SAR profiles for a series of homologous peptides with diverse activities. Furthermore, this research provides a solid foundation for the rational design of novel antimicrobial peptides.

Despite substantial heterogeneity of studies, there is evidence that antibiotics commonly used in primary care influence the composition of the gastrointestinal microbiota in terms of changing the composition and/or diversity. Benzyl isothiocyanate (BITC) from the food and medicinal plant nasturtium (Tropaeolum majus) is known for its antimicrobial activity and is used for the treatment against infections of the draining urinary tract and upper respiratory tract. Against this background, we raised the question whether 14 d nasturtium intervention (3 g daily, N=30 healthy females) could also impact the normal gut microbiota composition. Spot urinary BITC excretion highly correlated with a weak, but significant antibacterial effect against Escherichia coli. A significant increase in human beta defensin 1 as parameter for host defense was seen in urine and exhaled breath condensate (EBC) upon verum intervention. Pre-to-post analysis revealed that mean gut microbiome composition did not significantly differ between groups, nor did circulating serum metabolome. On an individual level, partly large changes were observed between sampling points, though. Explorative Spearman rank correlation analysis in subgroups revealed associations between gut microbiota and the circulating metabolome, as well as between changes in blood markers and bacterial gut species.

Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.

Silybum marianum is a therapeutic plant belonging to the family Asteraceae. It contains silymarin, as its principal component, and has been reported to demonstrate hepatoprotective activity. The study was aimed to investigate the phytochemical constituents, synthesis of nanoparticles, antioxidant activity and antimicrobial effects of the leaf extract. Extracts were synthesized from AgNO3 and characterized via FT-IR, U.V and XRD. The antioxidant activity was determined using DPPH, H2O2 and β-carotene assays. Similarly, all extracts expressed significant DPPH inhibition (IC50) of 5.1, 5.0, 4.7, 2.3, 4.3 and 1.1 (ug/mL), H2O2 of 1.3, 2.2, 4.7, 5.6, 4.0 and 1.0 (ug/mL) from the methanol/water extract, nanoparticles, n-Hexane, ETOAC, n-Butanol and Ascorbic acid (standard) respectively. The extract exerted scavenging activity on β-carotene with a significant IC50 inhibition of 1.5, 0.8, 5.2, 0.8, 2.7, 4.8 at 0 hour and 1.5, 0.8, 5.2, 0.8, 2.7 and 4.8 (ug/mL) after 2 hours water bath incubation at 50°C in the order of the extracts above. Additionally, nanoparticles and plant extracts significantly (p<0.0001) inhibited the growth of bacteria with mean zone of inhibition ranging 7-13 mm and 4-11 mm. This study demonstrated that extracts from different solvents of S. marianum possess significant antioxidant activity, as well as antimicrobial effects which are all concentration dependent. Thus, the result suggests that methanolic/water leaf extract of S. marianum could serve as a potential source of antioxidants and can be explored as a therapeutic agent in free radical induced diseases.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

Human Ribonuclease (RNase) 6 is a monocyte and macrophage-derived protein with potent an-timicrobial activity toward uropathogenic bacteria. The RNASE6 gene is heterogeneous in hu-mans due to the presence of single nucleotide polymorphisms (SNPs). RNASE6 rs1045922 is the most common non-synonymous SNP, resulting in a G to A substitution that determines an ar-ginine (R) to glutamine (Q) transversion at position 66 in the protein sequence. By structural analysis we observed that R66Q substitution significantly reduces the positive electrostatic charge at the protein surface. Here, we generated both recombinant RNase 6 -R66 and -Q66 protein variants and determined their antimicrobial activity toward uropathogenic Escherichia coli (UPEC), the most common cause of UTI. We found that the R66 variant, encoded by the major SNP rs1045922 allele, exhibited superior bactericidal activity in comparison to the Q66 variant. The higher bactericidal activity of R66 variant correlated with an increase in the protein lipopolysac-charide binding and bacterial agglutination abilities, while retaining the same enzymatic effi-ciency. These findings encourage further work to evaluate RNASE6 SNP distribution and its impact in UTI susceptibility.

Plants have been used in alternative medicine for centuries in the treatment of many diseases with the metabolites they contain. The goal of this work was to investigate the phenolic profile, antioxidant capacity and biological activity of I. helenium subsp. pseudohelenium extracts. Phe-nolic (HPLC) substances in leaf ethanol (L-EtOH), leaf pure water (L-PW), root ethanol (R-EtOH), and root pure water (R-PW) extracts of Inula helenium subsp. pseudohelenium plant were investi-gated. Also, in vitro the antimicrobial (hollow agar), antioxidant (DPPH, ABTS.+, FRAP, CU-PRAC), antiproliferative (MTT assay against HT-29, MCF-7 and L-929), and DNA (Agarose gel electrophoresis) protective activities of the samples were examined. Although gallic acid was not detected in the extracts, the presence of curcumin was detected only in EtOH extracts. L-EtOH exhibited the best antimicrobial activity. According to the antioxidant results, it was found that the L-EtOH extract had an activity profile close to the standard antioxidants in general. It was also found that the L-EtOH extract stabilized the DNA by disrupting the scavenging effect of H2O2+DMSO. According to the antiproliferative activity results, EtOH extracts exhibited the strongest effect, especially against MCF7. When evaluated in general terms, it was found that L-EtOH extract showed better activity than other extracts. It is important to conduct more in vivo and in vitro studies after isolating the active components of extracts e.g. L-EtOH, which have good effects in terms of biological activity.

The primary objective of this study is to synthesize, elucidate the structural properties, and ex-plore the biological activity of novel metal complexes derived from 6-methyl-2-thiouracil and 6-propyl-2-thiouracil. The paper outlines a synthesis method and assesses the antimicrobial activ-ity of newly formed Cu(II) and Pd(II) complexes with two substituted 2-thiouracil ligands. The structural attributes of these newly developed compounds are thoroughly discussed based on data derived from melting point analysis, MP-AES for Cu and Pd, UV-Vis, IR, ATR, 1H NMR, 13C NMR and Raman spectroscopy. The interpretation of the complex spectra is assisted by the data for 6-methyl-2-thiouracil and 6-propyl-2-thiouracil obtained from 1H-1H COSY, DEPT-135, HMBC and HMQC spectra. In addition, the antimicrobial activity of these complexes and the free ligands are assessed against both Gram-positive and Gram-negative bacteria, as well as yeasts.