Bacillus licheniformis produce several classes of antimicrobial substances which are mainly either peptides or proteins. Among of them bacteriocins - peptides or proteins of different structural composition including synthesized by bacteria ribosomally; non-ribosomally synthesized peptides and cyclic lipopeptides; exopolysaccharides. Different representatives of these classes act against Gram-positive, Gram-negative bacteria, fungal pathogens and amoebae cells. In this review, a detailed classification of antimicrobial substances produced by B. licheniformis based on their chemical structure and mode of the synthesis and activity is presented. For some (rather limited number) of secreted antimicrobials mechanism of their harmful effect on the target cells is established, however, for many of them it remains unknown. The antimicrobial activity for most substances was studied in vitro only, however some substances were characterized in vivo and are found practical applications in medicine and veterinary. The cyclic lipopeptides with surfactant properties are applied in industry. In this review, a special attention on antimycobacterials produced by B. licheniformis is made as a possible approach to combat multidrug resistant and latent tuberculosis. Indeed, a number of peptides and proteins revealed strong antimycobacterial activity. However, medical application of some bacteriocins with promising in vitro antimycobacterial activity is limited by their toxicity for animals and humans. In this connection, similarly with the enhancement of the antimycobacterial activity of natural bacteriocins using genetic engineering, reduction of the toxicity by the same approach looks feasible. A unique capability of B. licheniformis to synthesize and produce a bouquet of different antibacterial compounds allow to consider this organism as a universal natural vehicle for antibiotic substances in form of probiotic cultures strains to combat various types of pathogens including mycobacteria.

Carbapenems are considered for treating Klebsiella pneumoniae and other Enterobacteriaceae infections, especially if they are not susceptible to other generally prescribed antibiotics, i.e., if they show resistance. In such cases, antibiotic activity decreases, and most patients succumb to the infection. A better understanding of the disease pattern and resistance mechanisms could be gained by magnifying the genes that confer resistance to antibiotics. Therefore, studying the genes that confer resistance to carbapenems and any other antibiotics for that matter is indispensable for coming up with improved treatment options. This study included the analyses of co-resistance patterns between resistance genes-between drug classes and within the carbapenem-resistant genes, genomic context analysis of highly expressed carbapenem-resistant genes, and phylogenetic study of OXA-producing genes, plasmid incompatibility identification, and sequence type identification using MLST. The presence of ESBLs, MBLs, and SBLs across the downloaded genomes was studied. SHV-producing genes were found to co-occur with most of the resistant genes belonging to different drug classes. The plasmid incompatibility type IncFIB was found to be common among the highly expressed genes, and most of these genes were flanked by different families of insertion sequence (IS) elements. MLST study suggested that the presence of sequence types ST-11, ST-14, and ST-147 was common in the downloaded set of genomes.

Background: Advances in additive manufacturing and the development of antimicrobial biopolymers facilitate the production of critical medical devices with strong and safe biocidal properties. The purpose of this study was to assess the antimicrobial efficacy, safety, and longevity of a polylactic acid-based biopolymer supplemented with a copper-based composite additive. Methods: An antimicrobial polylactic acid-based biopolymer was tested against several inoculants including Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Material safety was evaluated according to international testing standards for in vitro cytotoxicity. Results: The main findings of the present investigation showed a strong and long-lasting biocidal effect of a polylactic acid-based biopolymer embedded with a copper-based composite additive against Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Furthermore, the cytotoxicity and safety assessment of the antimicrobial biopolymer was found to be “non-toxic” and safe for human skin contact. Conclusions: The present investigation showed that the antimicrobial biopolymer exhibits strong and long-lasting biocidal properties against an array of viral and bacterial inoculants.

Bee products have a millennial tradition in human use due to their numerous heal-ing properties. The paper presents the chemical characterization, antioxidant, anti-microbial and anti-inflammatory potential of royal jelly, apilarnil and propolis. These were obtained in the Banat area, Romania, in 2022. Royal jelly and apilarnil were analyzed in pure and lyophilized form and propolis in pure form and tincture. The percentage of moisture, dry matter, pH, acidity, content of impurities, sugars, proteins, ash, macro and micro minerals, total amino acids, polyphenols and flavo-noids were studied. The samples analyzed by us have a very well developed antiox-idant and according to the analysis of the mineral content of beekeeping products, an increased variability of macro and microminerals was determined, but also the lack of Pb in their composition. The flavonoid content of the samples was between 2.61519 mg QE/g sample for commercial pure apilarnil and 279.56115 mg QE/g sample for propolis harvested in 2021, and that of polyphenols between 0.63507 mg QE/g sample for natural royal jelly and 42.82186 mg QE/g sample in propolis with harvest in 2021. Propolis acts as a good antimicrobial and antiinflammatory agent, a fact that deserves to be researched in detail and exploited as a product with an ap-itherapeutic role for various microbial and inflammatory conditions.

The design of multifunctional microcarriers has attracted significant attention because they combine various functions within a single system. In this study, we developed a set of multi-layered hydrogel microcarriers, which were first loaded with chemotherapeutic curcumin (CUR), then using the layer-by-layer (LbL) technique, coated through a polyelectrolyte shell consisting of chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). As an outer layer with antimicrobial function, newly synthesised alkylene quaternary ammonium salt functionalised polyelectrolytes (A-QAS-PEs) were applied. For this purpose, poly(acrylic acid) (PAA) was decorated with dif-ferent hydrophobic side chains (n-hexane and n-dodecane side entities) and different degrees of substitution (m) of quaternary ammonium groups (abbreviated as PAA-C(O)O-(CH2)n-N+(CH3)3(m); n=6,12; m=8-14%). The grafting approach of PAA with the al-kylene quaternary ammonium salt moiety was performed under mild reaction conditions using Steglich esterification followed by quaternisation. The structure of antimicrobial decorated PAA was confirmed by 1H NMR and FTIR, and the mean diameter of all multifunctional microparticles was characterised by SEM. The viscoelastic properties of the functional layers were studied using QCM-D. The release of CUR from the microcarriers was described using a hybrid model, i.e., a combination of first-order kinetics and the Korsmeyer-Peppas model. The antimicrobial activity of functionalised PAA and multilayered CUR-loaded hydrogel microcarriers with quaternary am-monium function was assessed against Staphylococcus aureus and Serratia marcescens by the agar diffusion assay method. Only a limited inhibition zone of PAA was observed, but in the case of both antimicrobial decorated PAA and the corresponding multilayered nanocarriers, the inhibi-tory activity increase was achieved against both strains of bacteria.

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.

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.

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.

Prevalence of antimicrobial-resistant bacteria has become a major challenge worldwide. Methicillin-resistant Staphylococcus aureus (MRSA)—a leading cause of infections—forms biofilms on polymeric medical devices and implants, increasing their resistance to antibiotics. Antibiotic administration before biofilm formation is crucial. Raman spectroscopy was used to assess MRSA biofilm development on solid culture media from 0 to 48 h. Biofilm formation was monitored by measuring DNA/RNA-associated Raman peaks and protein/lipid-associated peaks. The search for an antimicrobial agent against MRSA biofilm revealed that Eugenol was a promising candidate as it showed significant potential for breaking down the biofilm. Eugenol was applied at different times to test the optimal time for inhibiting MRSA biofilms, and the Raman spectrum showed that the first 5 h of biofilm formation was the most antibiotic-sensitive time. This study investigated the performance of Raman spectroscopy coupled with Principal Component Analysis (PCA) to identify planktonic bacteria from biofilm conglomerates. Raman analysis, microscopic observation, and quantification of the biofilm growth curve indicated early adhesion from 5 to 10 h of incubation time. Therefore, Raman spectroscopy can help in monitoring biofilm formation on a solid culture medium and performing rapid antibiofilm assessments with new antibiotics during the early stages of the procedure.

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).

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 the present study, the physicochemical, antioxidant and antimicrobial properties of three medicinal plants - thyme, cotton thistle and hawthorn fruit from the Western Rhodope Mountains, Bulgaria were investigated. In the first stage, the physicochemical characteristics (moisture, ash, carbohydrates, proteins and vitamin C) of the three herbs were determined. In the second stage, four types of extracts (aqueous, oil, methanolic and ethanolic) from them were prepared and the total phenolic content, presence of phenolic compounds (flavonoids and phenolic acids), antioxidant activity and their antimicrobial properties were determined. Thyme was characterized by the highest ash, proteins and vitamin C contents. The hawthorn fruit was characterized by the highest moisture and carbohydrate contents. The 70% ethanolic extracts of the three herbs exhibited the highest levels of phenolics and consequently a pronounced antioxidant activity, compared to the other three types of extracts. The flavonoid quercetin-3-ß-glucoside was in highest concentration in the thyme and hawthorn fruit, while myricetin dominated in the cotton thistle. The phenolic acid content analysis showed a prevalence of rosmaric acid in thyme, whereas chlorogenic acid was detected in highest concentration in hawthorn fruit and cotton thistle. High antimicrobial potential of the ethanolic and methanolic extracts was observed.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

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.

Edible coating gels developed from the Aloe vera plant have been used as a traditional medicine for about 3000 years. Aloe vera contains 110 potentially active constituents from six different classes: chromone and its glycoside derivatives; anthraquinone and its glycoside derivatives; flavonoids; phenylpropanoids and coumarins; phenylpyrone and phenol derivatives; and phytosterols and others. Apart from medicinal uses, Aloe gels have an important role in food preservation as edible coatings. They provide an edible barrier for atmospheric gases and moisture, and help to reduce the respiration and transpiration of fresh produce, which helps to preserve its postharvest quality. To date, numerous studies have been conducted on the postharvest use of Aloe vera gel. The present review article summarizes and discusses existing available information about the chemical constituents, antimicrobial activity, and food preservative characteristics of Aloe vera.

The emergence of multi-drug resistant bacteria has severely increased the burden on the global health system, and such pathogen infections are considered a great threat to human well-being. Antimicrobial peptides, due to their potent antimicrobial activity and low possibility of inducing resistance, are increasingly becoming the focus of much interest. Herein, a novel dermaseptin peptide, named Dermaseptin-SS1 (SS1), was identified from a skin secretion-derived cDNA library of the South/Central American tarsier leaf frog, Phyllomedusa tarsius, using a ‘shotgun’ cloning strategy. Chemically-synthesised peptide SS1 was found to be broadly effective against Gram-negative bacteria with low haemolytic activity in vitro. A designed synthetic analogue of SS1, named peptide 14V5K, showed a lower salt sensitivity with more rapid bacteria-killing compared to SS1. Both peptides employed the membrane-targeting mechanism to kill Escherichia coli. The antiproliferative activity of SS1 and its analogues, against lung cancer cell lines, was found to be significant.

Millions of people use public transportation daily worldwide and frequently touch surfaces, thereby producing a reservoir of microorganisms on surfaces increasing the risk of transmission. Constant occupation makes sufficient cleaning difficult to achieve. Thus, an autonomous, perma-nent antimicrobial coating (AMC) could keep down the microbial burden on such surfaces. A photodynamic AMC was applied to frequently touched surfaces in buses. The microbial burden (colony forming units, cfu) was determined weekly and compared to equivalent surfaces in buses without AMC (references). The microbial burden ranged from 0 – 209 cfu/cm² on references and from 0 – 54 cfu/cm² on AMC. The means were 13.4 ± 29.6 cfu/cm² on references and 4.5 ± 8.4 cfu/cm² on AMC (p<0.001). The difference of microbial burden on AMC and references was al-most constant throughout the study. Considering a hygiene benchmark of 5 cfu/cm², the data yield an absolute risk reduction of 22.6 % and a relative risk reduction of 50.7 %. In conclusion, photo-dynamic AMC kept down the microbial burden, reducing the risk of transmission of microor-ganisms. AMC permanently and autonomously contributes to hygienic conditions on surfaces in public transportation. Photodynamic AMC therefore are suitable for reducing the microbial load and closing hygiene gaps in public transportation.

Rapid in vitro assessment of antimicrobial drug efficacy under clinically relevant pharmacokinetic conditions is an essential element of both drug development and clinical use. Here we present an overview of a novel integrated methodology for rapid assessment of such efficacy, particularly against emergence of resistant bacterial strains, as jointly researched by the authors in recent years. This methodology enables rapid in vitro assessment of antimicrobial efficacy of a single or multiple drugs in combination, following clinically relevant pharmacokinetics. The proposed methodology entails (a) automated collection of longitudinal time-kill data in an optical-density instrument; (b) processing of collected time-kill data with the aid of a mathematical model to de-termine optimal dosing regimens under clinically relevant pharmacokinetics for a single or mul-tiple drugs; and (c) in vitro validation of promising dosing regimens in a hollow fiber system. Proof-of-concept of this methodology through a number of in vitro studies is discussed. Future directions for refinement of optimal data collection and processing are discussed.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance, we are seeing an increased intersection of genomics, microbiology, and clinical epidemiology. Clear nomenclature for AMR gene families and pathogens is critical for communication. For CARD release version 3.0.3 (July 2019), we updated the entire CARD database to reflect the latest pathogen names. In total, we detected 48 name changes or updates, some of which reflect major changes in familiar names.

Multicomponent reactions (MCR) have been used to synthesis a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in discovery of drug . The understanding of structure-activity correlations that drive the development of new goods and technology, requires structural variety in these libraries. In current world, antibiotic resistance is a major ongoing problem which is developing a problematic scenario in public health. The implementation of isocyanide based multicomponent reactions uphold a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and fight against such concerns. This study discusses recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs in the near future.

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.

We aim to evaluate efficiency of two American surveillance systems for monitoring the spread of antimicrobial-resistant (AMR) gonorrhea among men who have sex with men (MSM) using the novel continuous-time agent-based model of gonorrhea transmission. The model was developed using the simulation modelling tool AnyLogic and accounts for susceptible and resistant strains of N. gonorrhoeae, symptomatic and asymptomatic infection and various routes of transmission between different anatomical sites. The model was calibrated using a Bayesian calibration approach. The surveillance systems are the Gonococcal Isolate Surveillance Project (GISP) and the enhanced Gonococcal Isolate Surveillance Project (eGISP). We calculated accuracy, sensitivity, specificity and estimation error for each surveillance system based on the number of isolates submitted in 2018. We also varied that number to see its effect on the outcomes. Our results show that the accuracy of eGISP was between 66% and 92%, while GISP demonstrates low accuracy between 44% and 48%. We also determined that increasing the number of isolates results in improved performance for eGISP, while GISP is not particularly sensitive to it.

This work examines dairy and sheep farmer attitudes toward antimicrobial use (AMU) in New Zealand. There is increasing public demand on livestock producers to reduce AMU in livestock. The demand stems from concerns about potential antimicrobial resistance (AMR) that could originate from food animals. There is limited practical data on farmer knowledge of AMU. An electronic survey was sent to dairy (n= 378) and sheep farmers (n= 551). Seventy-six dairy farmers (20%, n=76/378) returned the survey. Dairy farmers (69%) showed low levels of concern about antimicrobial resistance and awareness of the need to reduce AMU. Additionally, 76% of dairy farmers didn’t think it was possible to reduce AMU. Thirty-nine sheep farmers (7%, 39/551) returned the survey. 76% of sheep farmers were supportive of restricted use of AMU. The dairy and sheep farmers sourced most of the advice from veterinarians (&gt;90%), the livestock industry (&gt;80%) and their colleagues (&gt;70%). This study shows that farmers showed varied concerns about AMR and AMU. Moreover, sheep farmers were more amenable to increased restriction on AMU than dairy farmers. This study suggests that knowledge gaps in farmers may best be filled by veterinarian input.

In the present study, we aimed to determine the antimicrobial resistance and genetic structure of a population of S. aureus recovered from transient and persistent intramammary infections and nares/muzzles. We investigated the antimicrobial resistance of 189 S. aureus strains using a broad antimicrobial susceptibility profile. Furthermore, 107 S. aureus isolates were strain-typed using staphylococcal protein-A (spa) typing. Here, a great proportion of strains exhibited multidrug resistance to antimicrobials, including resistance to critically important antimicrobials, although no methicillin-resistant S. aureus strains were found. Our study did not strengthen the idea that extramammary niches (i.e., nares/muzzles) are an important source for S. aureus. A discrepancy in the antimicrobial resistance between S. aureus strains isolated from nasal/muzzles and milk samples was observed. Furthermore, S. aureus isolates from transient and persistent IMIs did not differ by spa typing, suggesting that the persistence of bovine IMIs was determined by cow factors. Thus, the high level of multidrug-resistant S. aureus found in the two herds studied together with the predominance of a well udder-adapted S. aureus strain may contribute to the history of the high prevalence of mastitis caused by S. aureus, leading to great animal and public health concerns.

Companion animals are increasingly being recognized as important contributors to the spreading of antimicrobial resistant bacteria. The present work aimed to measure the antimicrobial drug prescribing in dogs and cats in the Campania region, Italy by analyzing the Veterinary Electronic Prescriptions (VEPs) between 2019 and 2020. The medical records associated with antimicrobial drug prescription were collected considering the drug delivery (systemic or local) and the rationale for the treatment chosen. In the period under investigation, 166879 drugs were prescribed of which 129116 (73.37 %) were antimicrobial. A total of 83965 (65.03 %) antibiotics were prescribed to dogs, 40477 (31.35 %) to cats, and 4674 (3.62 %) to other companion animals. In dogs the 90.48 % of VEPs prescribed for systemic treatment included an antimicrobial Critically Important or Highly Important or Important for human medicine (WHO, 2018). The most widely commonly prescribed class were fluoroquinolones. The main prescribed antimicrobials were the metronidazole-spiramycin (29.71%), amoxicillin-clavulanic (19.58%), enrofloxacin and cephalexin in dogs (16.52 %) and enrofloxacin (22.64%) and amoxicillin-clavulanic acid (21.37 %) in cats. Based on the results the wide use of broad-spectrum or second-line antibiotics is emerged together with the use of the critically important antimicrobials for human medicine.

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

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.

Antimicrobial photodynamic therapy (aPDT) used to sterilize carious dentin may irritate the pulp tissues because of tissue-penetrating laser and singlet oxygen generation. This study aimed to assess the effects of aPDT on rat pulp tissues. A cavity formed in a rat maxillary first molar was treated with aPDT. The combined photosensitizer and laser irradiation conditions in the aPDT groups were as follows: methylene blue and 100 mW for 60 s, brilliant blue (BB) and 100 mW for 60 s, BB and 50 mW for 120 s, and BB and 200 mW for 30 s. Each cavity was treated with an all-in-one adhesive and filled with flowable resin. aPDT was not applied for the control. In each group, the rats were sacrificed on postoperative days 1 and 14, and thin sections of the treated teeth were prepared. Pulp tissue disorganization (PTD), inflammatory cell infiltration (ICI), and tertiary dentin formation (TDF) were evaluated. At 1 day evaluation, there were significant differences between the aPDT group and controls with respect to PTD and ICI. 14 days later, almost all specimens showed tertiary dentin formation. aPDT caused temporarily reversible injury to the rat dental pulp, which healed with tertiary dentin formation.

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern, phylogroups and genetic variation of E. coli isolates from raw milk, vegetable salad and ground meat samples. Methods: Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing, PCR and RAPD assays were used to determine the incidence rate, antimicrobial resistance pattern, phylogenetic groups and genetic diversity of the E. coli isolates. Results: E. coli isolates were highly resistant to amoxicillin (79.16%), trime-thoprim-sulfamethoxazole (70.83%), amoxicillin-clavulanic acid (62.50%), tetracycline (54.16%), chloramphenicol (54.16%), nitrofurantoin (54.16%), ampicillin (45.83%), streptomycin (45.83%), and kanamycin (33.33%); and completely susceptible to norfloxacin and azithromycin. 70.83% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. RAPD with UBC245 primer categorized the isolates into 11 clusters. A high level of genetic di-versity was found among the isolates; however, 33.3% of the isolates were grouped in a major cluster (R5). Conclusions: Antibiotic resistance patterns are randomly distributed among the ge-netic clusters. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamina-tion.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

There is a great interest in finding antioxidants and products with antimicrobial activities from natural sources. The aim of this study was to obtain and identify the phenolic components and organic acids from Camellia oleifera cake. In addition, their antioxidant and antimicrobial activities were also investigated. The purity of phenolic components and organic acids obtained were 94.1 ± 0.5% w/w and 96.0 ± 0.3% w/w, respectively. There are 15 phenolic components have been detected and identified by HPLC-ESI-MS. Oxalic, citric, acetic, malic, and succinic acids are found to be major organic acids. The phenolic components and organic acids both had good antioxidant capacity, evaluated by 4 antioxidant activity assays (hydroxyl radical scavenging, superoxide radical scavenging, 1,1-diphenyl-2-picryl-hydrazyl radical scavenging and lipid peroxidation inhibition). In addition, the phenolic components and organic acids exhibited significant inhibitory activity against bacteria Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and fungi Mucor racemosus, Aspergillus oryzae, Rhizopus stolonifer. The phenolic components and organic acids from C. oleifera cake both showed good antioxidant capacity and exhibited antimicrobial activities. These results may be useful for the future use of phenolic components and organic acids from C. oleifera cake.

With the growing demand for personal protective equipment (PPE) in the face of the pandemic events caused by SARS-COV-2, the opportunity arises for the development of materials with characteristics such as antimicrobial, antiviral, antifungal activity, etc. The use of polymeric nanocomposites based on polyester/copper offers an alternative of great interest due to the versatility of the raw material and the high efficiency of copper as an antimicrobial additive. In this study, textile fibers prototypes with different Cu nanoparticles (CuNP) content were produced using melt-spinning to obtain bi-component multifilament fibers, and melt-blowing to obtain non-woven fabrics. The prototypes were tested against different pathogenic microorganisms such as S. aureus, E. coli, and C. albicans. It was shown that bi-component fibers offer more excellent protection against pathogens, while non-woven fabric only shows activity against E. coli. It was possible to identify that the CuNP were confined exclusively in the outer cover of the bi-component fibers, using different analytical techniques, which may be associated with the increase in antimicrobial activity, compared to the fibers present in the non-woven fabric, even when they present the same CuNP content.

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.

The recently reported microbial natural product N-benzoyl-tryptophane (1) along with twenty-two diverse known bioactive compounds were isolated from the marine Aspergillus terreus LGO13 after its re-cultivation using liquid culture fermentation. Structures of the isolated compounds were established on the basis of HR-ESIMS 1D/2D NMR spectroscopy, and comparison with literature data. The antimicrobial, cytotoxicity, and antiviral activities of the microbial extract and the obtained compounds were investigated using a set of microorganisms, cervix carcinoma KB-3-1, non-small cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulation was employed to explore the theoretical targets of the isolated metabolites as anti-SARS-CoV-2 agents. Chaetominine (2) seemed to be a potential candidate against papain-like protease (PLpro), one of the viral proteins being aimed by recent research as a possible target of anti-covid agents. Inspired by the MD results, we accordingly assessed the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2. Fumitremorgin C (6) showed a high selectivity index (SI = 20.3), while chaetominine (2) and azaspirofuran A (9) showed moderate selectivity index (SI = 6.6 and 3.2, respectively). These results showed a promising antiviral activity of Fumitremorgin C against SARS-CoV-2 virus.

Urinary peptides are the products of systemic protein turn over which are excreted out of the body and hence can serve as an important biomarker for various pathophysiology. These peptides in other species of bovine have been reported to possess several bioactive properties. To investigate the potential of urinary peptides we generated a peptidome profile from the urine of Murrah Buffaloes (n=10). Urine samples were processed using &lt;10 kDa MWCO filter, filtrate obtained was used for peptide extraction using Solid Phase Extraction (SPE). Eluate, obtained after SPE was extracted using ethyl acetate and the peptide-containing aqueous phase was collected. We extensively assessed the antimicrobial properties of the urinary aqueous phase. The nLC-MS/MS of the aqueous phase from 10 animals resulted in the identification of 8165 peptides originating from 6041 parent proteins. 76 Proteases responsible for the release of these sequences from precursor proteins were also identified. We further analyzed these peptide sequences to identify bioactive peptides and classify them into anti-cancerous, anti-hypertensive, anti-microbial, and anti-inflammatory groups with a special emphasis on antimicrobial properties. With this in mind, we simultaneously conducted experiments to evaluate antimicrobial properties of urinary aqueous extract on three pathogenic bacterial strains S. aureus, E. coli, &amp; S. agalactiae.

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 &gt;4 to &gt;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.

Antimicrobial resistance (AMR) remains a challenge in Kenya, while the extent remains unknown. To assess the knowledge, cultural beliefs, practices, and behavioral patterns among multisectoral stakeholders in Kenya. The cross-sectional survey was conducted in August 2021 among farmers, animal health service providers and AMR researchers. Regional digital data collection tool developed by FAO was shared and responses obtained through mail, phone calls and direct interviews. Descriptive and inferential analysis were conducted. Antimicrobials were mostly sourced from agro-veterinary shops and from veterinary professionals. Farmers, often implement self-treatment and reported overuse, unnecessary use, and sometimes fail to complete the dosage in livestock. More farmers reported to have heard about antibiotics as compared to antimicrobials, mostly from friends and radio program, however only 9.2% could correctly differentiate the two. Animal Health Service Providers (AHSP) were the source of information to farmers regarding AMR. AHSPs mainly relied on suppliers and distributors for information about antibiotics. Both farmers and AHSPs treated viral infections with antibiotics. One Health Partners (OHPs) had higher knowledge and largely favorable attitudes towards AMR. Up to 72.7% of OHPs from training institutions had AMR included in training curriculum however, they were optimistic livestock farmers and government were less concerned about AMR. Gaps in knowledge and practice on Antimicrobial Stewardship (AMS) were observed in all categories of stakeholders. Given the documented knowledge-practice gap, innovative solutions are needed for both AHSPs and farmers to promote good antimicrobial stewardship practices and to mitigate burdens of AMR. Outcomes of this research should deepen the understanding of critical information and trigger behavioral change in usage and stewardship of antimicrobials.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).

The antiradical and antimicrobial activity of lignin and lignin-based films are both of great interest for applications such as food packaging additives. The polyphenol structure of lignin in addition to the presence of O-containing functional groups is potentially responsible for these activities. This study used DPPH assays to discuss the antiradical activity of HPMC/lignin and HPMC/lignin/chitosan films. The scavenging activity (SA) of both binary (HPMC/lignin) and ternary (HPMC/lignin/chitosan) systems was affected by the percentage of the added lignin: the 5% addition showed the highest activity and the 30% addition had the lowest. Both, scavenging activity and antimicrobial activity are depending on the biomass source showing the following trend: organosolv of softwood > Kraft of softwood > organosolv of grass. Testing the antimicrobial activities of lignins and lignin-containing films showed high antimicrobial activities against gram-positive and gram-negative bacteria at 35 °C and at low temperatures (0-7 °C). Purification of kraft lignin has a negative effect on the antimicrobial activity while storage has positive effect. The lignin release in the produced films affected the activity positively and the chitosan addition enhances the activity even more for both gram-positive and gram-negative bacteria. Testing the films against spoilage bacteria that grow at low temperatures revealed the activity of the 30% addition on HPMC/L1 film against both B. thermosphacta and P. fluorescens while L5 was active only against B. thermosphacta. In HPMC/lignin/chitosan films the 5% addition exhibited activity against both B. thermosphacta and P. fluorescens.

Due to nutritional benefits and perceived humane ways of treating the animals, the demand for antibiotic-free pastured poultry chicken has continued to be on a steady rise. However, despite non-usage of antibiotics in pastured poultry broiler production, antibiotic resistance (AR) is reported in zoonotic poultry pathogens. However, actors that drive multidrug resistance (MDR) in pastured poultry are not known. In this study, we used machine learning and deep learning approaches to predict farm management practices, and physicochemical properties of feces and soil that drive MDR in zoonotic poultry pathogens. Antibiotic use in agroecosystems is known to contribute to resistance. Evaluation of the development of resistance in environments that are free of antibiotics such as the all-natural antibiotic-free, pastured poultry production systems described here is critical to understand the background AR. We analyzed 1,635 preharvest (feces and soil) samples collected from forty-two pastured poultry flocks and eleven farms in the Southeastern United States. CDC National Antimicrobial Resistance Monitoring System guidelines were used to determine antimicrobial/multidrug resistance profiles of Salmonella, Listeria and Campylobacter. A combination of two traditional machine learning (RandomForest and XGBoost) and three deep learning (Multi-layer Perceptron, Generative Adversarial Network, and Auto-Encoder) approaches, identified critical farm/environmental variables that drive multidrug resistance in poultry pathogens, in broiler production systems that represents background resistance. This study enumerates management practices that contribute to AR and recommendations to potentially mitigate multidrug resistance and prevalence of Salmonella and Listeria in pastured poultry.

High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and Sinapis alba L. have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from grinded seeds, mainly sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumour and tumour cell lines was induced by S. alba seeds extract. To evaluate whether Sinapis spp effect was only due to glucosinolate content or it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to MAPKs modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumour cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

A derivative series of 3,4-dimethoxy-β-nitrostyrene were synthesized and identified including new compound 6. The effect of antimicrobial activity of 3,4-alkyloxy modification of β-nitrostyrene was investigated. A molecular docking was also performed to obtain information about their interactions with Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B containing cysteine 215 and arginine 221 as essential active residues plays a key role in signaling pathways that regulate various cell functions of microorganisms, which also act as negative regulator in signaling pathways of insulin that are involved in type 2 diabetes and other metabolic diseases. Compound 5 and 6 were the most potent as fragment of PTP1B inhibitor based on molecular docking, but compound 5 was more effective against Candida albicans. These compounds interact with serine 216 and arginine 221 residues. However, further research is needed to investigate their potential medicinal use.

The prevalence for chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by an aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at an improved management of infected wounds, a variety of wound dressings incorporating antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound care market. However, many wound care professionals agree that none shows comprehensive and optimal antimicrobial activity. This manuscript summarizes and discusses studies on novel PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall effi-cacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.their preparation, physical properties relevant in the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.

Interprofessional collaboration between general practitioners (GPs) and community pharmacists (CPs) is central to implement antimicrobial stewardship (AMS) programs in primary care. This study aimed to design a GP-pharmacist antimicrobial stewardship (GPPAS) model in Australian primary care. A seven-component exploratory study was conducted since 2017 to 2021 to inform a GPPAS model. We generated both secondary and primary evidence through a systematic review, a scoping review, a rapid review, nationwide surveys of Australian GPs and CPs including qualitative components and a pilot study of a GPPAS model. All study evidence was synthesised, reviewed, merged and triangulated to design a prototype GPPAS model using a Systems Engineering Initiative for Patient Safety theoretical framework. Secondary evidence informed effective GPPAS interventions, and primary evidence captured interprofessional issues, challenges and future needs to implement GPPAS interventions by GPs and CPs. A GPPAS model framework involving GP-pharmacist team-based five GPPAS sub-models were successfully designed to foster AMS education, antimicrobial audits, diagnostic stewardship, delayed prescribing, and routine review of antimicrobial prescription by improved GP-CP collaboration. A GPPAS model could be used as a guide to collaboratively optimise antimicrobial use by GPs and CPs. Implementation studies on GPPAS model and sub-models are required to integrate GPPAS model into GP-pharmacist interprofessional care models in Australia.

Few Sclerophyllous plants from the central coast of Chile have been systematically studied. This work describes the phytochemical composition and antimicrobial properties of Baccharis concava Pers. (sin. B. macraei), a shrub found in the first line and nearby the pacific coast between latitudes 29-38⁰S. B. concava has been traditionally used by indigenous inhabitants of today central Chile for their anthelmintic properties, wound healing properties and as a diuretic. Hydro-alcoholic extracts of B. concava were prepared from leaves and small branches. The qualitative phytochemical characterization indicated presence of alkaloids, steroids, terpenoids, flavonoids, phenolic and tannins compounds. The antimicrobial activity of this extract was assessed in a panel of microorganisms including Gram-positive, Gram-negative bacteria and pathogenic yeasts. The extract displayed important antimicrobial effects against Gram positive, Candida albicans, and Cryptococcus neoformans, but not against Gram negative, for which an intact Lipopolysaccharide (LPS) is apparently the determinant of resistant to B. concava extracts. The hydroalcoholic extract was then fractionated through a sephadex LH-20/methanol-ethyl acetate column. Followed, the fractions were pooled according to a similar composition that was visualized by TLC/UV analysis. Fractions obtained by this criterion were assessed for their antimicrobial activity against Staphylococcus aureus. The fraction presenting the most antimicrobial activity was HPLC-ESI-MS/MS analyzed obtaining a composition rich in structures derived from caffeoylquinic acid, dicaffeoylquinic acid and quercetin, among others. In conclusion, the extracts of B. concava show a strong antimicrobial activity probably due to their composition rich in metabolites derived from caffeoylquinic acid and quercetin, that in turn could be responsible for helping with wound healing, as reported from its ancient cultural use. In addition, the development of antimicrobial therapies based in the molecules found in B. concava could help to combat infection caused by pathogenic yeasts and Gram-positive bacteria, without affecting the Gram-negative microbiota.

Background: The use of medicinal plants and their effective compounds as natural sources that have antioxidant properties, has been considered by researchers. Antioxidants are compounds that effectively inhibit the reaction of oxygen and nitrogen-free radicals with biomolecules in a variety of ways, reducing damage or preventing cell death, cardiovascular diseases, and cancers. Objective: In this study, chemical compounds of Adiantum capillus-veneris essential oil were used to evaluate its antioxidant and antimicrobial activity using water distillation and gas chromatography. Methods: The whole plant was dried at room temperature at 25 ° C and the distillation method with water with modifications was used using a Clevenger device for essential oil extraction. Gas chromatography-mass spectrometry (GC/MS) was used to identify the resulting essential oil compounds and the antioxidant and antibacterial activity of the essential oil was evaluated. Results: The most important chemical constituents of Adiantum capillus-veneris essential oil were carvone (33.00%), carvacrol (15.05%), hexadecanoic acid (7.02%), hexahydrofarnesyl acetone (4.25%) and n-nonanal (4.2%). The antibacterial activity of Adiantum capillus-veneris essential oils (mg/ml) was calculated and the highest antibacterial activity was determined by Staphylococcus aureus (8.23±1.07), Streptococcus pyogenes (12.46±1.62), and Diphtheroid (11.37±1.36) at a concentration of 100 mg/ml of essential oils. Conclusion: The results of the present study showed that the essential oil of Adiantum capillus-veneris prevented the growth of three pathogenic bacteria. This antibacterial property is due to the presence of flavonoid compounds in Adiantum capillus-veneris has the capacity for therapeutic and medical uses.

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.

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.

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

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.

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.

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.

Antimicrobial resistance (AMR) is a recurring global problem, which constantly demands new antimicrobial compounds to challenge the resistance. It is well known that essential oils (EOs) have been known for biological activities including antimicrobial properties. In this study, EOs from seven aromatic plants of Asir region of southwestern Saudi Arabia were tested for their antimicrobial efficacy against four drug resistant pathogenic bacterial isolates (Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Streptococcus typhimurium) and one fungal isolate (Candida albicans). Chemical compositions of EOs were determined by Gas chromatography-Mass Spectrometry (GC-MS). The results revealed that EOs from Mentha cervina, Ocimum basilicum and Origanum vulgare proved most active against all isolates with inhibitory zone range between17 to 45 mm. The lowest minimum inhibitory concentration (MIC) of 0.025mg/ml was observed for Staph. aureus and Streptococcus pyogenes with EO of Origanum vulgare. All the three EOs showed significant anti candida activity. Together form the results the EOs from Mentha cervina, Ocimum basilicum and Origanum vulgare demonstrated a significant antimicrobial efficacy against drug resistant microorganisms.

Chenodeoxycholic acid (CA) is a naturally occurring bile acid that is produced in the liver from cholesterol. Three CA complexes using Zn(II), Mg(II), and Ca(II) ions were synthesized to examine the chelation tendencies of CA towards these metal ions. The complexation reaction of CA with the metal ions under investigation was conducted with a 1:1 molar ratio (CA to metal) at 60-70°C in natural media (pH 7-8), which consisted of a binary solvent of MeOH and H2O (1:1). The resulting CA complexes were characterized using analytical data (metal, H, C, and Cl, analysis) and spectral data (UV-visible, FT-IR, and 1H NMR) to elucidate the complexes’ structures. The results suggested that CA in anion form utilized oxygen atoms of the carboxylate group (-COO−) to capture Zn(II), Mg(II), and Ca(II) ions. This produced complexes with the general compositions of [Zn(CA)(H2O)Cl], [Mg(CA)(H2O)Cl]H2O, and [Ca(CA)(H2O)Cl]2H2O, respectively. The Kirby-Bauer disc diffusion assay was then used to explore the bioactivity of the CA complexes toward three fungal species, three Gram-positive bacteria, and two Gram-negative bacteria. The Ca(II) and Mg(II) complexes exhibited marked inhibitory effects on the cell growth of the fungal species Aspergillus niger with potency equal to 127% and 116% of the activity of the positive control, respectively. The Zn(II) and Ca(II) complexes strongly inhibited the growth of Penicillium sp., while the Zn(II) and Mg(II) complexes showed strong growth inhibition towards the Gram-negative species Pseudomonas aeruginosa.

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.

Two antimicrobial agents such as silver nanoparticles (AgNPs) and titanium dioxide (TiO2) have been formulated with natural polysaccharides (chitosan or alginate) to develop innovative inks for the rapid, customizable, and extremely accurate manufacturing of 3D printed scaffolds useful as dressings in the treatment of infected skin wounds. Suitable chemical-physical properties for the applicability of these innovative devices were demonstrated through the evaluation of water content (88-93%), mechanical strength (Young’s modulus 0.23-0.6 MPa), elasticity, and morphology. The antimicrobial tests performed against Staphylococcus Aureus and Pseudomonas Aeruginosa demonstrated the antimicrobial activities against Gram+ and Gram– bacteria of AgNPs and TiO2 agents embedded in the CH or ALG macroporous 3D hydrogels (AgNPs MIC starting from 5 µg/ml). The biocompatibility of chitosan was widely demonstrated by cell viability tests and was higher than that observed for alginate. Constructs containing AgNPs at 10 µg/ml concentration level did not significantly alter cell viability as well as the presence of titanium dioxide; cytotoxicity towards human fibroblasts was observed starting with AgNPs concentration of 100 µg/ml. In conclusions, the 3D printed dressings here developed own the features to be cheap, highly defined, easy to be manufactured and further applied in personalized antimicrobial medicine applications.

In two sequential replicates (n=90 and n=96 feedlot finisher cattle, respectively) we measured the impact of an Enterococcus faecium-based probiotic (DFM) and an altered feedlot pen environment on antimicrobial resistance among fecal enterococci in cattle fed (or, not fed) the macrolide tylosin. Diluted fecal samples were spiral-plated on plain and antibiotic-supplemented m-Enterococcus agar. In the first replicate, tylosin significantly (p&lt;0.05) increased the relative quantity of erythromycin-resistant enterococci. This effect was diminished in cattle fed the DFM in conjunction with tylosin. A similar observed effect was not statistically significant (P &gt; 0.05) in the second replicate. Isolates were speciated and resistance phenotypes were obtained for E. faecium and E. hirae. E. faecium isolates were whole-genome sequenced, which yielded sequence types (ST), resistance genes and phylogeny. Samples of the DFM were sequenced and found to contain E. faecium ST296, which was not present on Day 0 of either replicate. This DFM sequence type was found in fecal samples after Day 0, the majority of which were isolated from cattle in one of the DFM-fed pens. Increased prevalence of ST296 occurred with a concomitant decrease in ST240; of importance, the latter typically harbored both ermB and tet(M) genes.

Many marine animals use chemicals to defend themselves and their eggs from predators. Beyond their ecologically relevant functions, these chemicals may also have properties that make them beneficial for humans, including with biomedical and industrial applications. For example, some chemical defenses are also powerful antimicrobial or anti-tumor agents with relevance to human health and disease. One such chemical defense, Escapin, an L–amino acid oxidase in the defensive ink of the sea hare Aplysia californica, and related proteins have been investigated for their biomedical properties. This review details our current understanding of Escapin’s antimicrobial activity, including the array of chemicals generated by Escapin’s oxidation of its major substrates, L–lysine and L–arginine, and mechanisms underlying these molecules’ bactericidal and bacteriostatic effects on planktonic cells and the prevention of formation and removal of bacterial biofilms. Models of Escapin’s effects are presented, and future directions are proposed.

Antibiotics were once called miracle drugs which hit the market with astounding impact as it was considered the ultimate cure for infectious diseases in the mid-20th century. However, today nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperilling the foundation of modern medicine. During the COVID pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance. Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against MDR pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.

This study explored the potential synergism within chlorhexidine-silver nanoparticles conjugates against Influenza type A, Staphylococcus aureus, Escherichia coli, and Candida albicans. Silver nanoparticles (SN) were obtained by the reduction of silver ions with green tea total phenolic extract and conjugated with chlorhexidine (Cx). The particles were characterized by UV-Vis and FTIR spectroscopies, dynamic light scattering, X-ray diffraction, and transmission electron microscopy. A stable negatively-charged nano-silver colloid (ζ=-50.01) was obtained with an average hydrodynamic diameter of 92.34 nm. In the presence of chlorhexidine, the spectral data and the shift of the zeta potential to positive values (ζ=+44.59) revealed the successful sorption of the drug onto the silver surface. The conjugates (SN-Cx) demonstrated potentiation in the effects against S. aureus and C. albicans, and synergism against E. coli with minimal inhibitory concentrations of SN 5.5 µg/mL+Cx 8.8 µg/mL. The SN showed excellent, increasing with time, virucidal properties, and low toxicity. The coupling of the cationic chlorhexidine with nano-silver, however, did not reduce its intrinsic cytotoxicity on various cell lines (MDCK, BJ, and А549). The newly-synthesized antimicrobial agent presented with an extended and promising therapeutic spectrum and needs to be further evaluated on relevant to the designated route of administration three-dimensional cell models (e.g., nasal, bronchial, dermal, ocular, etc.).

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.

Selenocyanates form an interesting class of organic selenium compounds as they serve as multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl selenocyanates (1-13) have been synthesized and an insight into their structural properties using X-ray crystallography has been obtained. The compounds subsequently have been evaluated for their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds exhibit pronounced activity against various strains of bacteria (both Gram-positive and Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only non-mutagenic but also possess moderate cytotoxic activity against cancer cells.

The current study aims to produce a material that has a dual effect of healing and anti-inflammatory. For this target k-carrageenan/polyacrylamide hydrogel film loaded with cetrimide (k-CAR/PAAm/CI) was performed by manual casting technique. Definite concentrations of k-CAR and AAm was heated at 80°C for 2 hours, CI and glycerol were added. The solution was cast without using initiator and cross-linker. The reaction of the sulfonic acid group -SO3H of k-CAR with -CONH2 group of PAAm lead to the formation of a sulfonamide (-SO2NH-) linkage. The characteristics of the produced films were investigated by FTIR, TGA, contact angle, and mechanical properties. Improvement in the thermal stability was performed in k-CAR/PAAm/CI2 film containing 1.5% CI compared to the film has 0.5% CI (k-CAR/PAAm/CI1). The contact angle measurement proved the films are hydrophobic that enhanced by increasing CI content. The tensile strength and elongation percent values are considered adequate for materials used in wound care. k-CAR/PAAm/CI2 (1.5% CI) film showed superior antimicrobial activity against P. aeruginosa, moderate activity against S. aureus, and low activity against E. coli. The film k-CAR/PAAm/CI2 was effectively inhibiting the heat-induced hemolysis and may offer a promising approach for the development of effective wound dressings.

Natural products have long played a major role in medicine and science. The garden snail Cornu aspersa is a rich source of biologically active natural substances which might be an important source for new drugs to treat human disease. Based on our previous studies seven fractions containing compounds with Mw &lt;3 kDa, &lt;10 kDa, &lt;20 kDa, &gt;20 kDa, and between 3-5 kDa, 5-10 kDa, and 10-30 kDa were purified from the mucus of C. aspersa and analyzed by tandem mass spectrometry (MALDI-TOF/TOF). Seventeen novel peptides with potential antibacterial activity have been identified by de novo MS/MS sequencing using tandem mass spectrometry. The different fractions were tested for antibacterial activity against Gram─ (Pseudomonas aureofaciens and Escherichia coli) and Gram+ (Brevibacillus laterosporus) bacterial strains as well anaerobic bacterium Clostridium perfringens. These results revealed that the peptide fractions exhibit a predominant antibacterial activity against B. laterosporus, the fraction with Mw 10 – 30 kDa against E. coli, another peptide fraction &lt;20 kDa against P. aureofaciens, and the protein fraction &gt;20 kDa against the bacterial strain C. perfringens. The discovery of new antimicrobial peptides (AMPs) from natural sources is of great importance for public health due to their effective antimicrobial activities and low resistance rates.

Currently, metal nanoparticles have varied uses for different medical, pharmaceutical, and agricultural applications. Nano-biotechnology combined with green chemistry has great potential for the development of novel and necessary products that benefit human activities, while encourages the reduction of hazardous reagents for nanoparticle production. Green chemistry has an important role due to its contribution to unconventional synthesis methods of gold and silver nanoparticles from plant extracts, which have exhibited antimicrobial potential among other outstanding properties. Biodiversity-rich countries need to collect and convert knowledge from biological resources into processes, compounds, methods, and tools, which need to be achieved along with sustainable use and exploitation of biological diversity. Therefore, this review focuses on the importance of metal nanoparticles, the use of plant extract for their synthesis as well as other available methods, and the relevant antimicrobial activity that can be exploited in a sustainable model of agricultural management through a modern nanotechnological approach.

Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.

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.

One-dimensional nanostructures such as silver nanowires (AgNWs) have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties; however, their application in the prevention of infections linked to bone tissue regeneration interventions has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension and of completely preventing biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as it presents enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into potential clinical applications of these materials.

Background: In 2014 the World Health Organization (WHO) warned of an emerging world-wide crisis of antibiotic resistant microorganisms. In response, government and professional organizations recommended that health care systems adopt antimicrobial stewardship programs (ASPs). In the United States, the Centers for Medicare Services (CMS) mandated antimicrobial stewardship in the hospital inpatient setting. Effective January 1, 2020, the Joint Commission required ambulatory centers that prescribe antibiotics, such as wound centers, to institute an ASP. Chronic wounds often remain open for months, during which time patients may receive multiple courses of antibiotics and numerous antimicrobial topical treatments. The wound clinician plays an integral role in reducing antimicrobial resistance in the outpatient setting: antibiotics prescribed for skin and soft tissue infections are among the most common in an outpatient setting. One of the most challenging aspects of antimicrobial stewardship in treating chronic wounds is the inaccuracy of bacterial and infection diagnosis. Methods: Joint Commission lists five elements of performance (EP): (1) Identifying an antimicrobial stewardship leader, (2) establishing an annual antimicrobial stewardship goal, (3) implementing evidence-based practice guidelines related to the antimicrobial stewardship goal, (4) providing clinical staff with educational resources related to the antimicrobial stewardship goal, and (5) collecting, analyzing, and reporting data related to the antimicrobial stewardship goal. This article focuses on choosing and implementing an evidence-based ASP goal for 2020. Discussion: Clinical trials have demonstrated the ability of fluorescence imaging (MLiX) to detect clinically significant levels of bacteria in chronic wounds. Combined with clinical examination of signs and symptoms of infection, the MLiX procedure improves the clinician’s ability to diagnose infection and can guide antimicrobial use. In order to satisfy the elements of performance, the MLiX procedure was incorporated into the annual ASP goal for several wound care centers. Clinicians were educated on the fluorescence imaging device and guidelines were instituted. Collection of antimicrobial utilization data is underway.

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.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

The versatile one-pot green synthesis of a highly concentrated and stable colloidal dispersion of AgNPs was carried out using the self-assembled tannic acid without using any other hazardous chemicals. Tannic acid (Plant-based polyphenol) was used as a reducing and stabilizing agent for silver nitrate in a mild alkaline condition. The synthesized AgNPs were characterized for their concentration, capping, size distribution, and shape. The experimental results confirmed the successful synthesis of nearly spherical and highly concentrated (2281 ppm) AgNPs, capped with poly-tannic acid (AgNPs-PTA). The average particle size of AgNPs-PTA was found 9.90 ± 1.60 nm. The colloidal dispersion of synthesized nanoparticles was observed stable for more than 15 months in the ambient environment (25 oC, 65 % relative humidity). The synthesized AgNPs-PTA showed an effective antimicrobial activity against Staphylococcus Aureus Escherichia coli. Ag-PTA also exhibited enhanced catalytic properties. It reduces 4-nitrophenol into 4-aminophenol in the presence of NaBH4 with a normalized rate constant (Knor = K/m) of 615.04 mL·s-1·mg-1. Furthermore, AgNPs-PTA were stable for more than 15 months under ambient conditions. The unique core-shell structure and ease of synthesis render the synthesized nanoparticles superior to others, with potential for large-scale applications, especially in the field of catalysis and biomedical.

Extremely low concentrations of ciprofloxacin may select for antimicrobial resistance. A recent global survey found that ciprofloxacin concentrations exceded safe levels at 64 sites. We assessed if national median ciprofloxacin concentrations in rivers were associated with fluoroquinolone resistance in Escherichia coli. Methods Spearman’s regression was used to assess the country-level association between the national prevalence of fluoroquinolone resistance in E. coli and the median ciprofloxacin concentration in the countries rivers. Results The prevalence of fluoroquinolone resistance in E. coli was positively correlated with the concentration of ciprofloxacin in rivers (ρ=0.36; P=0.011; N=48). Conclusions Steps to reducing the concentrations of fluoroquinolones in rivers may help prevent the emergence of resistance in E. coli and other bacterial species.

Microbial diseases have been declared one of the main threats to humanity, which is why, in recent years, great interest has been generated in the development of nanocomposites with antimicrobial capacity. In the present work, two magnetic nanocomposites, based on Graphene Oxide (GO) and Multiwall Carbon Nanotubes (MWCNTs) were studied. The synthesis of these magnetic nanocomposites consisted of three phases: first, the synthesis of Iron Magnetic Nanoparticles (MNPs) was carried out in the presence of MWCNTs and GO using the Co-precipitation method. The second phase consisted of the adsorption of photosensitizer menthol-Zinc phthalocyanine (ZnMintPc) into MWCNTs and GO, and the third phase was the encapsulation in poly (N-vinylcaprolactam-co-poly(ethylene glycol diacrylate)) poly (VCL-co-PEGDA) polymer VCL/PEGDA a biocompatible hydrogel, in order to obtain the magnetic nanocomposites: VCL/PEGDA-MNPs-MWCNTs-ZnMintPc and VCL/PEGDA-MNPs-GO-ZnMintPc. In vitro studies were carried out using Escherichia coli and Staphylococcus aureus bacteria and the Candida albicans yeast based on the PTT/PDT effect. This research describes the optical, morphological, magnetic and photophysical characterizations of nanocomposites and their application as antimicrobial agents. It was evaluated the antimicrobial effect of magnetics nanocomposites based on the Photodynamic/Photothermal (PDT/PTT) effect; for this purpose, doses of 65 mW cm-2 at 630 nm of light were used. The VCL/PEGDA-MNPs-GO-ZnMintPc nanocomposite was able to eliminate colonies of E. coli and S. aureus, while VCL/PEGDA-MNPs-MWCNTs-ZnMintPc nanocomposite was able to eliminate the three types of microorganisms; consequently, the latter is considered a broad-spectrum of antimicrobial agent in PDT and PTT.

The approval of sucrose fatty acid esters (SFAEs) as food additives/preservatives has triggered enormous interest in discovering new applications for these materials. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species. The combination of chain length and site of acylation is crucial in endowing the SFAE with high antimicrobial potency against Aspergillus species. Following several important studies, we herein present the synthesis and an assessment of the effects of acylation site and chain length (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on the antimicrobial activity of mannopyranoside fatty acid esters. In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy, and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the structure-activity relationships (SAR). This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.

Current research in the field of antimicrobials is focused on the development of novel antibiotics and antimicrobial agents to counteract the huge dilemma that the human population is mainly facing in regards to the rise of bacterial resistance and biofilm infections. Host Defense peptides (HDPs) are a promising group of molecules for antimicrobial development as they share unique characteristics suitable for antimicrobial activity including their broad spectrum of activity and potency against bacteria. AamAP1 is a novel HDP that was identified through molecular cloning from the venom of the North African scorpion Androctonus amoeruxi. In vitro antimicrobial assays revealed that the peptide displays moderate activity against different strains of Gram-positive and Gram-negative bacteria. Additionally, the peptide proved to be highly hemolytic and displaying significantly high toxicity against mammalian cells. In our study, a novel synthetic peptide analogue named A3 was designed from the naturally occurring scorpion venom host defense peptide. The design strategy depended on modifying the amino acid sequence of the parent peptide in order to increase its net positive charge, percentage helicity and optimize other physico-chemical parameters involved theoretically in HDPs activity. Accordingly, A3 was evaluated for its in vitro antimicrobial and anti-biofilm activity individually and in combination with four different types of conventional antibiotics against clinical isolates of multi-drug resistant (MDR) Gram-positive bacteria. A3 was also evaluated for its cytotoxicity against mammalian cells. A3 displayed potent and selective in vitro antimicrobial activities against a wide range of MDR Gram-positive bacteria. Our results also showed that combining A3 with conventional antibiotics displayed a synergistic mode of action which resulted in decreasing the MIC value for A3 peptide as low as 0.125 µM. These effective concentrations were associated with negligible toxicities on mammalian cells. In conclusion, A3 exhibits enhanced activity and selectivity when compared with the parent natural scorpion venom peptide. The combination of A3 with conventional antibiotics may be pursued as a potential novel treatment strategy against MDR and biofilm forming bacteria.

Methyl Salicylate (MS), the principal constituent of Wintergreen oil (WO) was obtained from acetyl salicylic acid (ASA) by sequential transesterification-esterification reaction promoted by NbCl5for the first time. The reagents were added simultaneously, and the reaction process involved the transesterification and esterification reactions, which were accompanied by thin layer chromatography and gas chromatography. The conversion rate via GC was 100%, and the MS yield was 94%. A cytotoxicity of 50% and 64% for cultured S. aureus and metastatic melanoma cells, respectively, was observed for a concentration of 0.6 mg/mL, whereas no cytotoxicity for non-tumor cells was observed for this concentration, and it is considered to be the optimum concentration.

Antibiotic resistance represents a significant threat to the modern healthcare provision. The ESKAPEE pathogens, in particular, have proven to be especially challenging to treat, due to their intrinsic and acquired ability to rapidly develop resistance mechanisms in response to environmental threats. The development of biofilm has been characterised as an essential contributing factor towards antimicrobial-resistance and tolerance. Several studies have implicated the involvement of efflux pumps in antibiotic resistance, both directly, via drug extrusion and indirectly, through the formation of biofilm. As a result, the underlying mechanism of these pumps has attracted considerable interest due to the potential of targeting these protein structures and developing novel adjunct therapies. Subsequent investigations have revealed the ability of efflux pump-inhibitors (EPIs) to block drug-extrusion and disrupt biofilm formation, thereby, potentiating antibiotics and reversing resistance of pathogen towards them. This review will discuss the potential of EPIs as a possible solution to antimicrobial resistance, examining different challenges to the design of these compounds, with an emphasis on Gram-negative ESKAPEE pathogens.

The USDA-FSIS considers mechanically-tenderized beef as ‘non-intact’ and a food safety concern because of the potential for translocation of surface E. coli O157:H7 into the interior of the meat that may be cooked ‘rare or medium-rare’ and consumed. We evaluated 14 potential spray interventions on E. coli O157:H7-inoculated lean beef wafers (~10⁶ CFU/cm² , n=80) passing through a spray system (18 sec dwell time, ~40 PSI) integrated into the front end of a Ross TC-700MC tenderizer. Inoculated and processed beef wafers were stomached with D/E neutralizing broth and plated immediately, or were held in refrigerated storage for 1-, 7-, or 14 days prior to microbial plating. Seven antimicrobials that showed better performance in preliminary screening on beef wafers were selected for further testing on beef subprimals in conjunction with blade tenderization. Boneless top sirloin beef subprimals were inoculated at ~2 x 10⁴ CFU/cm² with a four-strain cocktail of Escherichia coli O157:H7 and passed once, lean side up, through an integrated spray system and blade tenderizer. Core samples obtained from each subprimal were examined for the presence/absence of E. coli O157:H7. Absence of E coli O157:H7 translocated into core samples correlated with the ability of the antimicrobials to reduce bacterial levels on the surface of beef prior to blade tenderization.

Sous-vide is a process in which food is vacuum-sealed and prepared in a water bath, heated to a precise temperature, and circulated in a sous-vide machine. This cooking technique is increasingly common in homes and catering establishments due to its simplicity and affordability. However, manufacturers' and chefs' recommendations for low-temperature and long-term sous-vide cooking in media raise food safety concerns, particularly when preparing beef tenderloin. In this study, Salmonella enterica was found to be inactivated by heat and sage essential oil (EO) in beef tenderloin from musculus psoas major that had undergone sous-vide processing. To determine whether heat treatment was likely to increase the sous-vide efficiency, S. enterica and sage EO were mixed. After being vacuum-packed and injected with S. enterica, the samples were cooked sous-vide for the prescribed time at 50, 55, 60, or 65 °C. On days 1, 3, and 6, the amounts of S. enterica, total bacteria, and coliform bacteria were measured in both groups of sous vide beef tenderloin. Mass spectrometry was used to identify bacterial strains on various days and categories. Each day that was measured, the test group exposed to a temperature of 50 °C for 5 minutes had a higher number of all microbiota. The most isolated microorganisms from the control and treated groups were Pseudomonas fragi, and in the treated group also S. enterica. It has been shown that adding sage essence oil (EO) in combination with the sous-vide gastronomic method leads to the stabilization and safety of beef tenderloin.

This study aimed to assess the impact of different modes of laser irradiation on the bactericidal efficacy of aPDT. Dentin plates were prepared by sectioning the crown dentin of bovine teeth infected with Streptococcus sobrinus. Nine aPDTs involving the combinations of three photosensitizers (brilliant blue, BB; acid red, AR; and methylene blue, MB) and three laser irradiation modes (50 mW for 120 s, 100 mW for 60 s, and 200 mW for 30 s) were performed for each infected dentin plate, and the control group consisted of the specimens not applied with aPDT. The bactericidal effects in 10 experimental groups were evaluated (n=11) using both assays of the colony-count and adenosine triphosphate (ATP). The data obtained were analyzed using the Kruskal-Wallis test. The aPDT performed with semiconductor laser in combination with BB, AR, and MB exerted a remarkable bactericidal effect. aPDT with MB exerted a more significant bactericidal effect in the colony-count assay. The results of aPDT performed with varying irradiation times and powers but with constant irradiation energy showed no difference with AR and MB between the modes, whereas BB showed a more significant bactericidal effect when irradiated for a shorter time at a higher irradiation power.

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.

It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

The botanical species Ceratonia siliqua L., commonly referred to as the Carob tree, and locally as “L’Kharrûb”, holds significance as an agro-sylvo-pastoral species, and is traditionally utilized in Morocco for treating a variety of ailments. This current investigation aims to ascertain the antioxidant, antimicrobial, and cytotoxic properties of the ethanolic extract of C. siliqua leaves (CSEE). Initially, we analyzed the chemical composition of CSEE through high-performance liquid chromatography with Diode-Array Detection (HPLC-DAD). Subsequently, we conducted various assessments, including DPPH scavenging capacity, β-carotene bleaching assay, ABTS scavenging, and total antioxidant capacity assays, to evaluate the antioxidant activity of the extract. In this study, we investigated the antimicrobial properties of CSEE against five bacterial strains (two gram-positive, Staphylococcus aureus, and Enterococcus faecalis; and three gram-negative bacteria, Escherichia coli, Escherichia vekanda, and Pseudomonas aeruginosa) and two fungi (Candida albicans, and Geotrichum candidum). Additionally, we evaluated the cytotoxicity of CSEE on three human breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-436) and assessed the potential genotoxicity of the extract using the comet assay. Through HPLC-DAD analysis, we determined that phenolic acids and flavonoids were the primary constituents of the CSEE extract. The results of the DPPH test indicated a potent scavenging capacity of the extract with an IC50 of 302.78 ± 7.55 µg/mL, which was comparable to that of ascorbic acid with an IC50 of 260.24 ± 6.45 µg/mL. Similarly, the β-carotene test demonstrated an IC50 of 352.06 ± 12.16 µg/mL, signifying the extract's potential to inhibit oxidative damage. The ABTS assay revealed IC50 values of 48.13 ± 3.66 TE µmol/mL, indicating a strong ability of CSEE to scavenge ABTS radicals, and the TAC assay demonstrated an IC50 value of 165 ± 7.66 µg AAE/mg. The results suggest that the CSEE extract had potent antioxidant activity. Regarding its antimicrobial activity, the CSEE extract was effective against all five tested bacterial strains, indicating its broad-spectrum antibacterial properties. However, it only showed moderate activity against the two tested fungal strains, suggesting it may not be as effective against fungi. The CSEE exhibited a noteworthy dose-dependent inhibitory activity against all the tested tumor cell lines in vitro. The extract did not induce DNA damage at the concentrations of 6.25, 12.5, 25, and 50 µg/ml, as assessed by the comet assay. However, the 100 µg/ml concentration of CSEE resulted in a significant genotoxic effect compared to the negative control. A computational analysis was conducted to determine the physicochemical and pharmacokinetic characteristics of the constituent molecules present in the extract. The Prediction of Activity Spectra of Substances (PASS) test was employed to forecast the potential biological activities of these molecules. Additionally, the toxicity of the molecules was evaluated using the Protox II webserver.

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.

Introduction. Bacterial resistance to antibiotics is estimated to cause the major number of deaths by 2050 if we do not find strategies to slow down the rise of drug resistance [1]. Reviews on Mediterranean Wild Edible Plants (MWEPs) with antimicrobial properties are scarce in the mean databases (Pubmed, Scopus and WoS). Hence, we proceeded to a new review of the studies on MWEPs. Methods. We used Wild Edible Plant and Antimicrobial as keywords. We only included the Mediterranean plants, and studies in non-Mediterranean countries, but for plants growing in Mediterranean basin. Exclusion criteria were the document type, studies not concerning plant, plants not edible, not antimicrobial properties, or totally out of topic. Results. Finally, the number of studies reviewed, starting from one hundred and ninety-two, was thirty-eight (19,8%), concerning the antimicrobial properties of seventy-four MWEPs species, be-longing to twenty-five Families. Fifty-seven (77%) out of seventy-four species, proved to be antimicrobial with a stringent threshold selection. Conclusions. The studies are still very heterogeneous. We still know too little about MWEPs properties, but what we already know seriously recommends continuing.

New Schiff base ofN'-((E)-3,3-diphenyl-2,3-dihydro-1H-inden-1-ylidene)-2-((Z)-2-oxoindolin-3-ylidene)hydrazine-1-carbothiohydrazide (HL) and its Co(II),Ni(II), Fe(III), Cu(II), Cd(II), Zn(II) and Mn(II) complexes were created, isolated, and characterized by analytical analysis in good yields of 60 to 90%, UV–Vis, magnetic measurements, molar conductivity, and FT-IR. Additionally, mass spectrometry was used to examine the new ligand complexes' structural characteristics.1H NMR spectroscopy and elemental analysis. Depending on the electronic spectra and magnetic susceptibility measurements, these complexes are predicted to have octahedral molecular geometry. As an example, the quantum chemical properties, bond lengths, and bond angles were discussed. The structural formula for the examined ligand was improved using the Gaussian09 tool. The DFT/B3LYP method was used to calculate the energy gaps and other crucial theoretical features. The prepared hydrazine ligand complexes Co (II), Ni (II), Fe (III), Cu (II), Cd (II), Zn (II) and Mn (II) complexes were evaluated for its antimicrobial properties. As antimicrobial agents, it was found that the organic ligand was less biologically active than the targeted complexes. Gram positive bacteria (3ty7-Staphylococcus), Gram negative bacteria (3t88-Escherichia coli), and fungi (5k04-Candida albicans) all have crystal structures that interact well with the chemicals in the title, according to molecular docking.

The development of multidrug resistance by pathogenic bacteria and yeast is a significant medical problem that needs to be addressed. One possible answer could be the combined use of antibiotics and silver nanoparticles, which have different mechanisms of antimicrobial action. Nanoparticles can be combined with antifungal agents in the same way. Biogenic silver nanoparticles synthesized using environmentally friendly technology using extracts of biologically active plants are an effective nanomaterial that needs to be comprehensively investigated for implementation into medical practice. In this study, the synergistic effects arising from their combined use with antibiotics and fungicides against various bacteria and yeasts, included in the ESKAPE list, were studied. Effective concentrations of substances were established, recommendations for the studied pathogenic species were presented and the effect of destruction of the bacterial membrane was illustrated. The most significant synergistic effect was manifested in pathogenic candida and brewer's yeast.

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.

Multidrug resistance (MDR) among gram-negative bacteria is a global public health threat because it has exhausted all standard therapeutic options. This has necessitated clinicians to reconsider colistin, an “old sort” antibiotic which was deemed toxic for clinical use. Unfortunately, swift resistance towards colistin by K. pneumoniae has been reported in different parts of the world. The study aimed at investigating the genetic determinants of colistin resistance in K. pneumoniae isolated from patients admitted in a tertiary care hospital in Kampala, Uganda. 31 archived multidrug resistant K. pneumoniae isolates obtained from rectal swabs of patients admitted to the Mulago Hospital ICU were retrieved. From this collection, we selected 7 colistin resistant K. pneumoniae isolates for whole genome sequencing and molecular profile analysis. In silico sequence data analyses were performed using established web-based bioinformatics tools. The sequence analysis of the genes involved in colistin resistance revealed several non-synonymous mutations in nucleotide sequences of pmrA, pmrB, phoP, phoQ and mgrB genes. Insertion transposase genes for the insertion sequences IS1 and IS5 which are highly implicated in colistin resistance via modification or inactivation of mgrB gene were identified in all isolates and were located in the chromosomal DNA at different genomic positions. No plasmid-borne mcr genes were detected. More so, the strains harbored numerous multidrug resistant genes. This study underscores the need of genomic surveillance of K. pneumoniae strains to limit further spread of colistin resistance genes to avert the potential risk of pandrug resistance. And high throughput sequencing is imperative.

Antimicrobial resistance (AMR), the capacity of microbial pathogens to survive in the presence of antimicrobials, is considered one of the greatest threats to human health worldwide and is growing rapidly in importance. AMR is thought to be driven in part by the use of antimicrobials (AMU) in livestock production. AMU reduction in agriculture is therefore important, but doing so may endanger farmers’ incomes and hamper broader food security. Understanding drivers for farmers' antibiotics use is essential to designing interventions which avoid harming agricultural output and safeguard farmers’ economic security. In this study, we analyse AMUSE survey data from poultry farmers in Senegal to explore the effects of vaccination, attitudes towards AMR, and biosecurity practices on: AMU, animal mortality, and farm productivity. We found that farmers with more “AMR-aware” attitudes may be less likely to use antibiotics in healthy birds. Stronger on-farm biosecurity was associated with less use of antibiotics in healthy birds, and in some specifications was linked to higher broiler productivity. Vaccination and AMU were both linked with higher disease prevalence, and both factors appeared conducive to higher broiler productivity. Overall, there is evidence that awareness-raising and biosecurity improvements could encourage prudent use of antibiotics, and that biosecurity and vaccination could to some extent replace antibiotic use as productivity-enhancing and disease-management tools in broiler farms. Finally, issues of farm antimicrobial stewardship must be considered at the structural level, with farm behaviours contingent on interaction with state and private stakeholders.

BackgroundIt is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals plays a role. MethodsWe used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. ResultsThe prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ=0.55; P<0.001], K. pneumoniae [ρ=0.58; P<0.001]; A. baumanii [ρ=0.54; P=0.004]; P. aeruginosa [ρ=0.48; P=0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. ConclusionsReducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various gram negative bacterial species.

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.

Antimicrobial use (AMU) is one of the major drivers of emerging antimicrobial resistance (AMR). Surveillance of AMU, a pillar of AMR stewardship (AMS), helps devise strategies to mitigate AMR. This descriptive, longitudinal retrospective study quantified the trends in human antibiotic utilization between 2010 and 2016 using data on all antibiotics imported for systemic human use into Tanzania's mainland. Regression and time series analyses were used to establish trends in antibiotics use. A total of 12,073 records for antibiotics were retrieved, totaling 154.51Daily Defined Doses per 1,000 inhabitants per day (DID) with a mean (± standard deviation) of 22.07 (±48.85) DID. The private sector contributed 93.76%% of utilized antibiotics. The top-ranking antibiotics were amoxicillin, metronidazole, tetracycline, ciprofloxacin and cefalexin. The DDIs and percentage contribution of these antibiotics were 53.78 (34.81%), 23.86 (15.44), 20.53 (13.29), 9.27 (6.0) and 6.94 (4.49), respectively. The time series model predicted significant increase in utilization(p-value =0.002). The model forecasted that by 2022, the total antibiotics consumed would reach 89.6 DIDs, corresponding to a 13-fold increase compared to 2010. Government intervention to curb inappropriate antibiotic utilization to mitigate the rising threat of antibiotic resistance should focus on implementing AMS programs in pharmacies and hospitals in Tanzania.

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.

(1) Background: Antimicrobial resistance (AMR) requires urgent multidisciplinary solutions, and Pharmacovigilance (PV) has the potential to strengthen current antimicrobial stewardship (AMS) strategies. This study aimed to characterise AMR-relevant adverse drug reaction (ADR) reports submitted to The Netherlands Pharmacovigilance Centre (Lareb); (2) Methods: We carried out a descriptive analysis of ADR reports submitted to Lareb, coded with AMR-relevant MedDRA Preferred Terms (PTs).; (3) Results: Between 1998 and Jan 2019, 252 AMR-relevant ADR reports were submitted to Lareb. The most frequent antibiotics were tobramycin (n=89; 35%), colistin (n=30; 11,9%), ciprofloxacin (n=16; 6,35%), doxycycline (n=14; 5,5%) and aztreonam (n=12; 4,76%). The most frequently used PTs were drug ineffective (n=71; 28%), pathogen resistance (n=14; 5%) and drug resistance (n=13; 13%). A total of 119 reports (74%) suggested use-related issues. Watch antibiotics were in 54% of the reports and Reserve antibiotics were in 19%. In the Watch group, “Off label use” and “Product use in unapproved indication” were the most frequent PTs and majority of reports on Reserve antibiotics were coded as “Off label”. (4) Conclusions: Addressing AMR using the PV methods will provide an opportunity for PV expansion and could encourage further investment in both in AMS programs and PV systems.

Melanins are phenolic polymers synthesized by most of the living organisms. This pigment is mainly attributed to provide photoprotection to the organism while it was found that pigment have immense bioactivities which could be utilized in day-to-day life ranging from sun screens lotions to solar cells. This pigment produced mainly via DOPA or homogentisate in bacteria. Melanin production is usually triggered by stress condition in bacteria. Marine bacteria have been reported as good melanin producers. In this study marine bacteria capable of melanin production were isolated from sea water of Kutch region, Gujarat using tyrosine basal media. The bacteria were identified using microscopic, biochemical and molecular techniques. Melanin produced by the bacteria is extracted and purified and further characterized using physicochemical techniques. Cosmetic properties of melanin like photoprotection, antioxidant and antimicrobial properties are evaluated.

Klebsiella pneumoniae, a major cause of both hospital and community-acquired infections, is listed by the World Health Organization as a critical priority antibiotic- resistant bacterial pathogen. With the appearance of sequencing techniques such as Next-generation Sequencing (NGS), there is the possibility to obtain the whole genome of the bacteria, getting to know all antimicrobial resistance determinants. The purpose of this study has been to apply this new technology to clinical microbiology, in order to characterize the resistome present in carbapenem-resistant K.pneumoniae strains isolated in a tertiary hospital in Valencia, Spain. A total of 234 isolates were prepared for whole-genome sequencing with Ilumina MiSeq, and sequences were later studied for antimicrobial resistance genes, sequence-typing and plasmids. Sequence-typing showed four major circulating clones in our hospital settings: ST11, ST307, ST101 and ST147, carrying different plasmids and different resistance determinants such as OXA-48 and NDM-1 carbapenemase. Application of new technologies such as whole-genome sequencing in clinical microbiology gives advantages when it comes to rapid therapy adjustment, consequently improving the patient’s clinical outcomes.

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.

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.