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

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.

Antimicrobial resistance (AMR) has become a worldwide health problem. Consequently, there is a global interest in the study of the antimicrobial activity of natural compounds as an alternative to antibiotics. One of the possibilities studied during the last years is the use of bacteriophages and their derived proteins. More specifically, phage lytic proteins or endolysins are specific enzymes that cause cell lysis and can be easily produced and purified after overexpression in bacteria. However, one of the major disadvantages of these proteins is their sensitivity to some environmental conditions that can reduce their efficiency. The use of vesicles for endolysin encapsulation could help overcome this disadvantage, offering an additional protection to the protein and allowing its controlled release and long-term stability.

Pollen, a remarkably versatile natural compound collected by bees for its abundant source of proteins and nutrients, represents a rich reservoir of diverse bioactive compounds with noteworthy chemical and therapeutic potential. Its large range of biological effects has been known and exploited since ancient times. Today, there is an increased interest in finding natural compounds agaisnt oxidative stress, a factor that contributes to various diseases. Recent research has unraveled a multitude of biological activities associated with bee pollen, ranging from antioxidant, anti-inflammatory, antimicrobial, and antifungal properties to potential antiviral and anticancer applications. Comprehending the extensive repertoire of biological properties across various pollen sources remains a challenge. By investigating a spectrum of pollen types and their chemical composition, this review produces an updated analysis of the bioactive constituents and the therapeutic prospects they offer. The findings of this review emphasize the necessity for further exploration and standardization of diverse pollen sources and bioactive compounds that could contribute to the development of innovative therapies.

Antibiotic resistance is now a first-order health problem, which makes the development of new families of antimicrobials an imperative. These compounds should ideally be inexpensive, readily available, highly active and non-toxic. Here we present the results on the antimicrobial activity of a series of natural and synthetic polyamines with different architectures (linear, tripodal and macrocyclic) and their derivatives containing the oxygen containing aromatic functional groups 1,3-benzodioxol, ortho/para phenol or 2,3-dihydrobenzofuran. The new compounds were prepared through a non-expensive process and their activity was tested against selected strains of yeast, gram-positive and gram-negative bacteria. In all cases, the conjugated derivatives showed antimicrobial activity higher than the unsubstituted polyamines. Several factors, such as the overall charge at physiological pH, the lipophilicity and the topology of the polyamine scaffold were relevant to their activity. The nature of the lipophilic moiety was also determinant on human cell toxicity. The lead compounds showed to be bactericidal and fungistatic, and they were synergic with the commercial antifungals fluconazole, cycloheximide and amphotericin B against the yeast strains tested.

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.

A series of pyrazolopyrimidines derivatives 4– 11 were synthesized using 1-(6-(3-methoxyphenyl)-4-methylpyridazin-3-yl)-1H-pyrazolo [3,4-d] pyrimidin-4-amine 3 as a starting material. The detailed synthesis, structure assignments of the novel compounds based on chemical and spectroscopic evidence, spectroscopic data, pharmacological properties and molecular docking are reported. The pharmacological evaluation illustrated that many of these compounds have good analgesic, anti-inflammatory and antimicrobial activities.

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), Contact lenses, Dental Applications, AMP-Incorporated Bone Grafts, Urinary tract infections (UTIs), Medical Implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

Oxidized sucrose (OS) reacts with amino group-containing polysaccharides, including chitosan, without catalyst, resulting in hydrogels entirely composed of carbohydrates. The presence of imine bonds with low structural stabilities and unreacted aldehydes in the structures of these hydrogels hinder their application as biomaterials. Therefore, herein, the chitosan hydrogels (CTSGs) obtained after the crosslinking of chitosan with OS were reduced using sodium borohydride to convert imine bonds to secondary amines and aldehydes to alcohols. Structures of CTSGs were comprehensively characterized by Fourier transform infrared and 13C nuclear magnetic resonance spectroscopies, and results implied that the degree of crosslinking (CR) depended on the OS feed amount used during CTSG preparation. Properties of CTSGs were significantly dependent on CR; with an increase in CR, thermal stabilities and dynamic moduli of CTSGs increased, whereas their swelling properties decreased. CTSGs exhibited antimicrobial properties against the gram-negative bacterium Escherichia coli, and their performances were also dependent on CR. Results indicated the potentials of CTSGs completely based on carbohydrates as antimicrobial hydrogels for various medical and pharmaceutical applications. We believe that this study will contribute to the development of hydrogels for application in the food, medical, and pharmaceutical fields.

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.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

This study presents a straightforward electrochemical and plasma deposition method for producing Cobalt-doped Blue-TiO2 nanotubes with enhanced catalytic properties. After a titanium plate has been anodized, specific procedures are carried out that cause oxygen vacancies to form inside the TiO2 nanostructures. The obtained catalysts were subjected to electrochemical tests (to identify charge transfer resistance and flat band potential), optical analysis (to determine the band gap and Urbach energy) and also characterized in terms of morphology, wettability and antibacterial effect in order to understand and analyze the impact of the Co doping method on the final catalyst characteristics. A hydrophilic film with star-shaped structures and with antibacterial effect was created when cobalt was electrochemically doped to Blue-TiO2 nanotubes. By using this electrochemical doping technique, the Urbach energy was raised from 1.171 to 3.836 eV while the band gap energy was decreased from 3.04 to 2.88 eV. Additionally, photodegradation experiments using artificial doxycycline (DOX) water were conducted to determine the practical relevance of the research findings. In areas like antimicrobial applications and photodegradation of DOX, these extra experiments aimed to show the practical applicability and potential advantages of the research findings.

In this study, composite nanofiber films comprising polyvinyl alcohol, wheat gluten, and glucose (PWG) were fabricated using electrospinning, followed by cross-linking via the Maillard cross-linking. Various mass concentrations of ferulic acid (FA) were incorporated into the PWG films. The results indicate that the average diameter of the FA-PWG films decreased from 449 nm to 331 nm as the concentration of FA increased, until reaching a concentration of 12%, after which a significant increase in diameter was observed. Subsequent Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) results suggested that FA was distributed in the sample films in an amorphous form through hydrogen and ester bonds. Additionally, release experiments and antimicrobial tests on FA-PWG sample films showed good con-trolled release of FA and excellent anti-Escherichia coli and Staphylococcus aureus activity of this film. These findings all indicate that the FA-PWG nanofiber film is a potential candidate for food active packaging.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research, to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in literature.

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.

Human exposure to antimicrobial resistance (AMR) through food is now very imperfectly understood, creating a significant gap in the design of interventions. The interchange of AMR genes and the transfer of AMR bacteria from animals to humans through the food chain necessitate comprehensive methods to risk reduction. With a focus on AMR in bacterial species isolated from food products, foods (of both animal and non-animal origin), and ambient samples, the current meta-analysis gathered up-to-date information on the epidemiology of AMR in animal-source food chain. As a result, the combined prevalence of AMR across the various food sources was calculated. From the 18,784 food samples obtained as a result of selected publications, 7,676 (40.9%) samples were contaminated, including 4343 (56.6%) and 3363 (43.4%) samples from Taiwan and India, respectively. Meat (chicken, pork, and beef), fish and milk all have moderate to medium potential for AMR exposure to both Gram-positive and Gram-negative foodborne pathogens such S. aureus, Clostridium, E. coli, Salmonella, etc. Antibiotic resistance to β-lactam, fluoroquinolone, carbapenem etc, is present in the majority of food samples. The results of this study emphasize the persistent danger of antimicrobial residue in animal-derived foods in Taiwan, India, and other nations with comparable customs.

Antimicrobial resistance (AMR) is a major global concern; antibiotics and other regular treatment methods have failed to overcome the increasing number of infectious diseases. Bacteriophages (phages) are viruses that specifically target/ kill bacterial hosts without affecting other human microbiome. Phage therapy provides optimism in the current global healthcare scenario with a long history of its applications in humans that has now reached various clinical trials. Phages in clinical trials have specific requirements of being exclusively lytic, free from toxic genes with an enhanced host range that adds an advantage to this requisite. This review explains in detail the various phage engineering methods and their potential applications in therapy. To make phages more efficient, engineering has been attempted using techniques like conventional homologous recombination, Bacteriophage Recombineering of Electroporated DNA (BRED), clustered regularly interspaced short palindromic repeats (CRISPR)-Cas, CRISPY-BRED/Bacteriophage Recombineering with Infectious Particles (BRIP), chemically accelerated viral evolution (CAVE), and phage genome rebooting. Phages are administered in cocktail form in combination with antibiotics, vaccines, and purified proteins, such as endolysins. Thus, phage therapy is proving to be a better alternative for treating life-threatening infections, with more specificity and fewer detrimental consequences.

Nutrigenomics is the study of the interaction of nutrition and genes, focusing on the influence of nutrients on the genome, proteome, and metabolome, and how nutrition affects human health. In the context of nutrigenomics, bioactive components are dietary ingredients that may transmit information from the external environment and alter gene expression in the cell, and hence the overall function of the organism. It is critical to consider food not only as a source of energy and essential nutrients necessary for life and growth, but also as a factor impacting health/disease, biochemical processes, biochemical pathway activation and affecting the diversity of the gut microbiome. Antimicrobial resistance in pathogenic and commensal microorganisms has emerged as a major public health concern due to emerging antimicrobial resistance genes in E. coli isolates from pig, cattle, chicken, and turkey meat, against tetracycline, streptomycin, and sulfonamides. Also, Salmonella spp. and Campylobacter spp. have shown antibiotic resistance at farms and slaughterhouses, and in animal-based food products. A correlation has been proven between a critical nutrient-responsive signaling system and catabolite control of gene expression, and a two-component signaling system that drives antibiotic resistance in E. faecalis, revealing a previously unknown integration between the nutritional status of the cell and intrinsic antibiotic resistance. Moreover, different nutrigenomic approaches can be applied to mitigate possible emergence of antimicrobial resistance against novel antibiotics. However, little progress has been achieved in converting nutrigenomics information into clinical advice, so far.

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.

Research and development on innovative packaging materials have advanced significantly to safeguard packaged food against microbial contamination and oxidation. To combat demanding issues, active packaging has evolved as a viable method for minimizing oxidation/microbial growth in packaged goods, extending their shelf life, and ensuring the consumer's safety. Active food packaging includes O2, CO2 scavengers, moisture absorbers, U.V. barriers, and carriers of antioxidant and antimicrobial agents. Various antimicrobial agents are carried and/or incorporated into food packaging formulations. Consumers demand natural antimicrobials over chemical/synthetic ones, such as bacteriocins, bacteriophages, and essential oils. Bacteriophages (viruses) have emerged as a feasible option for decontaminating and eliminating infections from food sources. These viruses can target specific food-borne pathogens without impairing beneficial bacteria and, most critically, without causing disease in humans or animals. Fortifying bacteriophages into food packaging films will not only kill specific food microorganisms but has evolved as a new weapon to combat antimicrobial-resistant (AMR) issues. The present review summarises recent developments in active antimicrobial packaging focused particularly on bacteriophage-food packaging applications and advantages, drawbacks, and future trends for active food packaging.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

Antimicrobial peptides (AMPs) are essential components of innate immunity across all species. AMPs have become the focus of attention in recent years as scientists are addressing antibiotic resistance, a public health crisis that has reached epidemic proportions. This family of peptides are a promising alternative to current antibiotics due to their broad-spectrum antimicrobial activity and tendency to avoid resistance development. A subfamily of AMPs interact with metal ions to potentiate their antimicrobial effectiveness, as such they have been termed metalloAMPs. In this work, we review the scientific literature of metalloAMPs that enhance their antimicrobial efficacy when combined with the essential metal ion, zinc (II). Beyond the role played by Zn(II) as a cofactor in different systems, it is well-known that this metal ion plays an important role in innate immunity. Here, we classify the different types of synergistic interactions between AMPs and Zn(II) into three distinct classes. By better understanding how each class of metalloAMPs uses Zn(II) to potentiate their activity, researchers can begin to exploit these interactions in the development of new antimicrobial agents and accelerate their use as therapeutics.

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.

The World Health Organization has identified antimicrobial resistance as a public health emergency and developed a global priority pathogens list of antibiotic-resistant bacteria that can be summarized in the acronym ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales species), reminding us of their ability to escape the effect of antibacterial drugs. We previously tested new heteroaryl-ethylene compounds in order to define their spectrum of activity and antibacterial capability. Now, we focus our attention on PB4, a compound with promising MIC and MBC values in all conditions tested. In the present study, we evaluate the activity of PB4 on selected samples of ESKAPE isolates from nosocomial infections: 14 S. aureus, 6 E. faecalis, 7 E. faecium, 12 E. coli and 14 A. baumanii. Furthermore, an ATCC control strain was selected for all species tested. MICs were performed according to the standard method, with some modifications. PB4 MIC values were within very low ranges regardless of bacterial species and resistance profiles: from 0,12 to 2 mg/L for S. aureus, E. faecalis, E. faecium and A. baumannii. For E. coli, the MIC values obtained were slightly higher (4-64 mg/L), butstill promising. The PB4 heteroaryl-ethylenic compound was able to counteract the bacterial growth of both high-priority Gram-positive and Gram-negative clinical strains. In the future, it would be interesting to evaluate the activity of PB4 in animal models to test for its toxicity.

Bacterial vaginosis (BV), the most common cause of vaginal discharge, is characterized by a shift in the vaginal microbiota from lactobacillus dominance to a diverse array of facultative and strict anaerobic bacteria which form a multi-species biofilm on vaginal epithelial cells. The rate of recurrence after therapy is high, often >60%. While the BV biofilm itself likely contributes to recurrent and/or refractory disease after treatment by reducing antimicrobial penetration, antimicrobial resistance in BV-associated bacteria including those, both within the biofilm and the vaginal canal, may be the result of independent, unrelated bacterial properties which are discussed in this paper. Our current recommendations for the treatment of refractory and recurrent BV are also provided.

Antimicrobial peptides (AMPs) are considered as promising alternatives to conventional antibiotics in order to overcome the growing problems of antibiotic resistance. Computational prediction approaches receive an increasing interest to identify and design the best candidate AMPs prior to the in-vitro tests. In this study, we focused on the linear cationic peptides with non-hemolytic activity, which are downloaded from the Database of Antimicrobial Activity and Structure of Peptides (DBAASP). Referring to the MIC (Minimum inhibition concentration) values, we have assigned a positive label to a peptide if it shows antimicrobial activity; otherwise the peptide is labeled as negative. Here, we focused on the peptides showing antimicrobial activity against Gram-negative and against Gram-positive bacteria separately, and we created two datasets accordingly. Ten different physico-chemical properties of the peptides are calculated and used as features in our study. Following data exploration and data preprocessing steps, a variety of classification algorithms are used with 100-fold Monte Carlo Cross Validation to build models and to predict the antimicrobial activity of the peptides. Among the generated models, Random Forest has resulted in the best performance metrics for both Gram-negative dataset (Accuracy: 0.98, Recall: 0.99, Specificity: 0.97, Precision: 0.97, AUC: 0.99, F1: 0.98) and Gram-positive dataset (Accuracy: 0.95, Recall: 0.95, Specificity: 0.95, Precision: 0.90, AUC: 0.97, F1: 0.92) after outlier elimination is applied. This prediction approach might be useful to evaluate the antibacterial potential of a candidate peptide sequence before moving to the experimental studies.

We present a simple strategy to generate a family of carbon dot/iron oxide nanoparticles (C/Fe-NPs) that relies on the thermal decomposition of iron (III) acetylacetonate in the presence of a highly fluorescent carbon-rich precursor, while polyethylene glycol serves as the passivation agent. By varying the molar ratio of the reactants, a series of C/Fe-NPs have been synthesized with tuneable elemental composition in terms of C, H, O, N, Fe. The quantum yield is enhanced from 6% to 9% as the carbon content increases from 27% to 36%, while the room temperature saturation magnetization is improved from 4.1 emu/g to 17.7 emu/g as the iron content is enriched from 17 to 31%. In addition, the C/Fe-NPs show excellent antimicrobial properties, minimal cytotoxicity and demonstrate promising bioimaging capabilities, thus showing great potential for the development of advanced diagnostic tools.

Medicinal plants have antibacterial, antifungal and antiviral activities. More or less all plants have medicinal properties. In this research article, we have selected four economically important plants (three fruit plants and an economically important plant), Malus domestica Borkh., Prunus persica L., Ricinus communis L., and Carica papaya L. found in several areas of Indian state Uttarakhand. Using the methanolic extract of leaves, we have screened those four plants against four human pathogenic bacteria, Escherichia coli, Streptococcus pneumoniae, Staphylococcus aureus and Micrococcus luteus. For our experiment we have screened the methanolic leaf extracts of four plants against the above-mentioned bacteria. Statistical analysis was also performed for validation. Result revealed the said bacteria have potential antibacterial activities. So, these leaves can be used for clinical trial. These plants can also be used for making herbal medicines.

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.

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.

The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.

Background: The study describes the comparison of different microbial load results of natural falling and dipping of the house fly (Musca domestica) in water and milk to investigate the possibilities of preventing the effect of the transferred pathogens from the house fly to our sources by pointing out the existence of antimicrobial factors within the house fly. Methods: Samples of house fly were collected from Jeddah and Makkah (Makkah region) and were directly transferred to the laboratory. Each house fly was packed in sterile test tubes. Each tube was opened oppositely to a larger test tube containing 10 ml of sterile tap water, and sterile water at pH 4.0 in other similar series of treatments to represent the reactions of stomach fluids. Later, the house flies were left for 20 seconds after reaching the water surface, and then cultured on different microbial media to evaluate the microbial load of the natural falling of the house fly. To evaluate the complete dipping of house flies in the water, two methods were tested by one complete dip for the flies for 20 seconds, and three times complete dipping for 20 seconds in water before evaluating the microbial load. The same methods were achieved on milk in a series of experiments and the microbial load was evaluated after the incubation at room temperature for three hours. Results: It was found that dipping treatments of house flies gave lower microbial contamination in water at pH 4.0 than neutral pH. The lower microbial load was also observed when dipping the house flies three times in water as compared to once dipping and natural falling treatments. It was also found that the complete dipping of house flies’ treatments in milk will reduce the microbial contamination as compared to natural falling treatments. Conclusion: The observed results support the presence of antimicrobial factors on the house fly.

Salmonella remains one of the notable food-borne bacterial pathogens. It is associated with poultry and poultry products including eggs. This study investigated Salmonella distribution in eggshell and content, their antimicrobial resistance pattern, and the possible risk factors driving contamination in Ogun State, Nigeria. A total of 500 eggs (5 eggs pooled into one sample) were collected and culturally examined for the presence of Salmonella serovars. Isolates were further characterized biochemically using Microbact 20E (Oxoid) and Antimicrobial susceptibility determined by the Kirby-Bauer disk diffusion method. A total of 14 Salmonella isolates spread across 10 serovars were recovered from the 100 pooled egg samples; 10 (10%) from the market and 4 (4%) farms, 13(13%) eggshell, and 1(1%) egg content. All tested serovars were susceptible to ampicillin, chloramphenicol, florfenicol, and kanamycin. Resistance was mostly observed in sulfamethoxazole 8 (80%), followed by ciprofloxacin 5 (50%) and tetracycline 3 (30%). Sales of eggs in the market appears to be a strong factor encouraging contamination in addition to poor biosecurity and unhygienic handling of eggs on the farm.

Campylobacter is one of the major foodborne pathogens of concern in its growing trend of antimicrobial resistance. C. jejuni and C. coli are the major causative agents, with C. jejuni contributing to most of the cases in approximately 90% in the world. Infection is transmitted to humans due to consumption of contaminated food and water. Campylobacteriosis caused by C. jejuni is commonly presented with severe diarrhoea, abdominal pain, fever, headache, nausea, and vomiting with some extreme cases resulting in Guillain–Barré syndrome (GBS) and acute flaccid paralysis. Symptoms are severe in cases of children below 5 years, elderly and individuals who are immunocompromised. The infection is usually sporadic, and self-limiting and thus does not require antibiotics for treatment. Still, the antimicrobial resistance in Campylobacter is a major concern because of the transmission of resistance from animal sources to humans. This review highlights the recent epidemiology, geographical impact, resistance mechanisms, spread of Campylobacter spp. and the strategies to control the transmission of Campylobacter from veterinary sources and its antimicrobial resistance.

Pathogenic Neisseria gonorrhoeae causes the sexually-transmitted infection gonorrhea. N. gonorrhoeae has evolved high levels of antimicrobial resistance (AR) leading to therapeutic failures even in dual-therapy treatment with azithromycin and ceftriaxone. AR mechanisms can be acquired by genetic transfer from closely related species, such as naturally-competent commensal Neisseria species. At present, little is known about the antimicrobial resistance profiles of commensal Neisseria. Here, we characterized the phenotypic resistance profile of four commensal Neisseria species (N. lactamica, N. cinerea, N. mucosa, and N. elongata) against 10 commonly used antibiotics, and compared their profiles to 4 N. gonorrhoeae strains, using disk diffusion and minimal inhibitory concentration assays. Overall, we observed that 3 of the 4 commensals were more resistant to several antibiotics than pathogenic N. gonorrhoeae strains. Next, we compared the penicillin-binding-protein 2 (PBP2) sequences between commensal and N. gonorrhoeae strains. We found mutations in PBP2 known to confer resistance in N. gonorrhoeae also present in commensal Neisseria sequences. Our results suggest that commensal Neisseria have unexplored antibiotic resistance gene pools that may be exchanged with pathogenic N. gonorrhoeae, possibly impairing drug development and clinical treatment.

This review was carried out to identify different beta-lactamase resistance genes reported in published literature from Nigeria and to determine the proportion estimates of the important beta-lactamase resistance genes in Nigeria. Sixty-three (63) articles were included in this review based on the eligibility criteria. All the beta-lactamases reported were detected from the Gram-negative bacteria, most especially from Enterobacteriaceae (n=53). Thirty-six different beta-lactamase genes have been reported from Nigeria. These genes belong to the narrow-spectrum, AmpC, extended-spectrum, and carbapenemase beta-lactamase resistance genes. Eight (8) genes (bla_DHA, bla_CTXM-1, bla_CTXM-14, bla_GES-1, bla_VEB-1, bla_OXA-1, bla_OXA-2, and bla_TEM-1) were shared between animals and humans, 5 genes (bla_SHV-1, bla_SHV-2, bla_SHV-11, bla_SHV-12, and bla_NDM-1) were common to both humans and environment while none of the genes was unique to both animals and environment. Four genes including bla_CMY, bla_TEM-1, bla_AmpC, and internationally pandemic bla_CTXM-15 gene were unique to animals, humans, and the environment. No carbapenemase gene was reported from animals yet. The pooled proportion estimate of ESBL genes in Nigeria was 31% (95% CI: 26-36%, P<0.0001), while the estimate of bla_CTXM-15 gene in Nigeria was 46% (95% CI: 36-57%, P<0.0001). The proportion estimate of AmpC genes was 32% (95% CI: 11-52%, P<0.001), while the estimate for carbapenemases was 8% (95% CI: 5-12%, P<0.001). This study has provided information on the beta-lactamases distribution in Nigeria. This is necessary for a better understanding of molecular epidemiology of clinically important beta-lactamases especially the extended-spectrum beta-lactamases and carbapenemases in Nigeria.

Betadine (Providone-Iodine) solution is a topically applied antiseptic, which has been used for wound care and surgery for decades for the prevention and treatment of skin and wound infections. However, several studies have documented the ineffectiveness of Betadine solution. Other topical antimicrobial dressings, including those that contain silver, have been used in the management of infected wounds. The present study was undertaken to determine if the combination of 5% Betadine solutions and silver colloidal gel (Ag-gel), is more effective than the individual materials in inhibiting the growth of both Gram negative and Gram positive bacteria. These determinations were carried out by both the colony forming unit (CFU) assay, and confocal laser scanning microscopy (CLSM). Ag-gel showed complete inhibition on all the bacteria, except Klebsiella pneumoniae CI strain while 5% Betadine concentrations did not completely kill any of the tested bacteria. However, K. pneumoniae was completely eliminated in the presence of the combination of 5% Betadine solution plus Ag-gel. Confocal laser microscopy confirmed the CFU results. Thus this study demonstrated that while the individual treatments are not effective in killing all the bacteria tested, the combination of 5% Betadine solution and Ag-gel completely kill all bacteria tested, including K. penumoniae CI.

Tabebuia aurea (Silva Manso) Benth. & Hook. f. The ex S.Moore (yellow ipe), belonging to the Bignoniaceae family, used in the popular for fever, inflammation and healing of skin wounds. The extract was prepared by maceration, using 70% ethanol. Through HPLC analysis, it was possible to identify substances, mainly phenolic, such as lapachol, present in Bignoniaceae. The phenolic content was 21.36 mg / Eag in the antioxidant activity, the effective concentration of 50% was 53.03 ± 1.14 µg / mL. The antimicrobial activity against S.aureus, E. coli and C. albicans was evaluated by microdilution in broth, which verified action against the tested microorganisms. Cell viability has been inhibited for tumor cells, although this has not been observed for normal cells. The LD50 against A.aegypti mosquito larvae was 3504.6 mg / L and there was no mortality in the concentration tested for the snail B.glabrata. Nontoxic or low toxicity for A. salina and T. molitor, respectively, and did not exhibit hemolytic action at concentrations of antibacterial effect. Given the above, it was concluded that the bark extract of the studied species has bioprospecting potential for the future development of antimicrobial products.

Environmental interventions and ecological adaptations harbor millions of valued substances and metabolites in plants which can be employed and commercialized for human benefits. Present study encompasses the untapped potential of pine needles of Indo-Himalayan region for the production of different metabolites and their pharmacological significance in terms of antioxidant and antimicrobial activity. Total phenolic and flavonoid content from the needles of ten pine species was quantified using three different solvent systems. Results revealed that out of 10 different selected Pinus species, Pinus taeda showed highest concentration of total phenolics, soluble-F phenolics and flavonoids content (approx.147.02 mg/g, 141.08 mg/g and 21.91mg/g respectively) as compared to other species. On the other hand P. greggii showed highest Bound-W phenolic content (approx.3.62mg/g). Among all the selected plant species, the needles of P.echinata exhibited the highest and P.thunbergii had the lowest ratio of total flavonoids to total phenolics. Most of these compounds were found to have effective antioxidant activities as well as antimicrobial activity, as estimated by oxygen radical absorbance capacity (ORAC) and disk diffusion test respectively.

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.

This study aimed to screen the antibacterial activity of essential oils from different parts (leave and stem) of Salvia officinalis against some Gram positive and Gram negative bacteria using agar disc diffusion test, then the extracts were prepared by hydro distillation to extract the essential oils. Maceration and hexane extraction by Soxhlet were used to obtain crude extracts from the leave and stem. Essential oils from the leaves and the ethyl acetate extract of the leaves showed higher antimicrobial activity, while hexane extract of leaves and stems showed moderate antibacterial activity. In contrast the essential oil from the stems showed very low antibacterial activity. It was observed that the results gram positive bacteria (staphylococcus aureus) was more sensitive than Gram negative (Echerichia coli).

Background: Infections caused by E. coli cause considerable disease burden and range from frequently occurring and relatively innocent urinary tract infection (UTI) to severe bloodstream infection (BSI). The incidence of infections caused by ESBL-producing E. coli (ESBL-PEc) is increasing, justifying surveillance and development of preventive strategies in several domains. Faecal carriage is universal and believed to be the most important reservoir for E. coli from which infections can originate. It is currently unknown to what extent Dutch E. coli carriage strains in the community reflect isolates causing disease. In this study, we will perform comparative genomics to infer the population structures of human-derived ESBL-PEc from community- and hospital-acquired infections and from community-based faecal carriage samples in the Netherlands. Furthermore, we will describe the molecular epidemiology of E. coli isolates causing invasive disease (BSI). Methods: This study uses four different microbiological data sources: 1) ESBL-PEc from patients with community-acquired UTI tested in primary care between May and November 2017, 2) ESBL-PEc from urine cultures obtained from patients hospitalized between January 2014 and December 2016, 3) E. coli from blood cultures obtained from patients hospitalized between January 2014 and December 2016, and 4) ESBL-PEc from faecal samples collected in a national population- prevalence study performed between January 2014 and January 2017. Clinical epidemiological data was collected from all patients and all isolates were subjected to whole genome sequencing. Discussion: The EPIGENEC study (EPIdemiology and GENetics of E. coli) will describe the molecular epidemiology of E. coli BSI and assess the genomic population structure of ESBL-PEc strains from community-acquired and nosocomial infections, and of ESBL-PEc reflecting community-based faecal carriage. Information from these studies may assist in optimizing surveillance strategies and determining targets and potential impact of future new preventive measures.

(1) Background: Factors reported in literature associated with inappropriate prescribing of antimicrobials, such as physicians with less experience, uncertain diagnosis, and patient caregiver influences on physicians' decisions. Monitoring antimicrobial resistance is critical for identifying emerging resistance patterns, developing, and assessing the effectiveness of mitigation strategies. Improvement in prescribing `antimicrobials would minimize the risk of resistance and, consequently, improve patients' clinical and health outcomes. The purpose of the study is to delineate factors associated with antimicrobial resistance, describe the factors influencing prescriber’s choice during prescribing of antimicrobial, and examine factors related to consequences of inappropriate prescribing of antimicrobial. (2) Methods: Cross-sectional study conducted among healthcare providers (190) in six tertiary hospitals in the Eastern province of Saudi Arabia. The research panel has developed validated and piloted survey specific with closed-ended questions. A value of P &lt;0.05 was considered for statistical significance. All data analysis was performed using Statistical Package for Social Sciences (IBM SPSS version 23.0). (3) Results: 72.7% of the respondents have agreed that poor skills and knowledge are key factors that contribute to the inappropriate prescribing of antimicrobials. All the respondents acknowledged effectiveness and previous experience with the antimicrobial, and reading scientific materials (such as books, articles, and the internet) were key factors influencing physicians’ choice during antimicrobial prescribing. (4) Conclusion: The current study has identified comprehensive education and training needs for healthcare providers about antimicrobial resistance. Using antimicrobials unnecessarily, insufficient duration of antimicrobial use, and using broad spectrum antimicrobials, were reported to be common practices. Further, poor skills and knowledge were a key factor that contributed to the inappropriate use and overuse of antimicrobials and using antimicrobials without physician prescription (self-medication) were the key factors which contribute to AMR from participants’ perspectives. Furthermore, internal policy and guidelines are needed to ensure that the antimicrobials are prescribed in accordance with standard protocols and clinical guidelines.

This service improvement project was carried out at LEKMA Hospital, Ghana. Ghana has high levels of antimicrobial resistance (AMR). There is an urgent need to introduce models of care that optimize antibiotic prescribing. Methods Delayed / back-up prescribing is a strategy that could reduce antibiotic use in suspected upper respiratory tract infections. Four different models of delayed / back-up prescribing [no prescription; post-dated prescription (given to patient); post-dated prescription (forwarded to pharmacy); and follow-up appointment for reassessment after 3 days] were implemented in discussion between clinician and patient. Patients were contacted 10 days after their appointment to record compliance, check on their wellbeing, and rate their experience. Results Over a 3-month period (12/2019-02/2020), 142 patients were eligible for delayed / back-up prescribing. The most common clinical diagnoses were sore throat (102/140, 73%), common cold (22/140, 16%) and sinusitis (10/140, 7%). In total, 12 (9%) patients remained symptomatic at day 10, and only one individual in the entire cohort took antibiotics. Most patients (95%) rated their experience as good or very good. Conclusions Delayed / back-up prescribing models can lead to substantial reduction in antibiotic consumption amongst outpatient department patients with suspected upper respiratory tract infections. Delayed / back-up prescribing can be implemented safely in low and middle-income countries.

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.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Infection-related cardiovascular diseases (CVDs) represent a significant health challenge, necessitating novel therapeutic strategies targeting key receptors involved in inflammation and infection. Antimicrobial peptides (AMPs) offer a promising approach, potentially disrupting pathogenic processes. This study aimed to investigate the efficacy of AMPs as therapeutic agents by examining their interactions with critical CVD-related receptors. A comprehensive computational approach was utilized to assess the interactions between AMPs and receptors associated with CVDs. Molecular docking studies were conducted to evaluate AMP binding to target receptors: ACE2, CRP, MMP9, NLRP3, and TLR4. The top-performing AMPs were further analyzed through 100 ns molecular dynamics (MD) simulations, and their binding affinities were quantified using MM/PBSA calculations. The analysis revealed that Tachystatin, Pleurocidin, and Subtilisin A exhibit strong binding affinities to key CVD-related receptors, including ACE2, CRP, and MMP9. These AMPs demonstrated the potential for disrupting receptor-peptide interactions critical to infection and inflammation. MD simulations confirmed the stability of AMP-receptor complexes, with MM/PBSA calculations showing significant binding energies. Future directions include conducting in vitro and in vivo studies to validate the therapeutic efficacy and safety of these AMPs in clinical settings.

The rapid evolution of drug resistance is one of the greatest health issues of the 21st century. There is an alarming situation to find new therapeutic strategies or candidate drugs to tackle ongoing multi-drug resistance development. The marine environment is one of the prime natural ecosystems on Earth, the majority of which is still unexplored, especially when it comes to the microbes. A wide variety of bioactive compounds have been obtained from a varied range of marine organisms, however, marine bacteria-produced bacteriocins are still undermined. Owing to the distinct environmental stresses that marine bacterial communities encounter, their bioactive compounds frequently undergo distinct adaptations that confer on them a variety of shapes and functions, setting them apart from their terrestrial counterparts. The ribosomally-synthesized and posttranslationally modified peptides (RiPPs), bacteriocins are of special interest because of their variety in structure and diverse potential biological activities. Additionally, the gut microbiome of marine creatures are largely unexplored source of new bacteriocins with promising activities. There is a huge possibility of novel bacteriocins from marine bacterial communities that might come out as efficient candidates to fight against antibiotic resistance, especially in light of the growing pressure from antibiotic-resistant diseases and industrial desire for innovative treatments. The present review summarizes known bacteriocins from marine bacteria, evolutionary aspects, challenges, and huge possibilities of unexplored bacteriocins from marine bacterial communities.

Antimicrobial peptides (AMPs) are regarded as a promising alternative to traditional antibiotics in the face of ever-increasing resistance. Our research has focused on crotalicidin (Ctn), an AMP from a snake venom, and a fragment thereof, Ctn[15-34], with improved in vitro antimicrobial and anticancer activities and remarkable serum stability. As the retroenantio versions of both AMPs maintained favorable profiles, in this work we evaluate the in vivo efficacy of both the na-tive-sequence AMPs and their retroenantio counterparts in a murine infection model with Aci-netobacter baumannii. A significant reduction in bacterial levels is found in the mice treated with Ctn[15-34]. However, contrary to expectations, the retroenantio analogues either exhibit toxicity or lack efficacy when administered to mice.

Wetlands are ecosystems that are essential to ecological balance and biodiversity, never-theless human activity is a constant threat to them. Excess nutrients are caused by inten-sive livestock and agricultural operations, pollution, and population growth, which in turn leads to uncontrolled microbiological development. This impairment in water quality can constitute a risk to animal, human, and environmental health. To thoroughly charac-terize the microbial communities, shotgun metagenomics was used to characterize the taxonomic and functional pattern of microorganisms that inhabit urban wetlands in the Los Lagos Region of Chile. The main objective was to identify microorganisms of veteri-nary relevance, assess their potential antibiotic resistance, and characterize the main vir-ulence mechanism. As expected, a high diversity of microorganisms was identified, in-cluding bacteria described as animal or human pathogens. Also, a diverse repertory of an-timicrobial-resistant genes (ARGs) was detected, which confers mainly resistance to be-ta-lactams, consistent with the families of antibiotics most used in Chile. Besides, a di-verse collection of virulence mechanisms was also identified. Given the significance of the relationship between environmental, animal, and human health—a concept known as One Health—there is a need to establish molecular surveillance programs. This work is the first report of the presence of these harmful biological elements in urban wetlands subjected to anthropogenic pressure, located in the south of Chile.

The application of antimicrobials in aquaculture primarily aims to prevent and treat bacterial infections in fish. Inappropriate use of antimicrobials in fish farming may result in the emergence of zoonotic antibiotic-resistant bacteria and subsequent transmission of resistant strains to humans via food consumption. From recently, AMR emerged as a significant public health concern in the aquaculture ecosystem and fisheries. The aquatic environment serves as a potential reservoir for resistant bacteria, with aquaculture practices providing an ideal breeding ground for AMR due to the excessive use of antimicrobials to prevent and treat diseases. The mutual inter-connection of intensive fish farming systems with terrestrial environments, food processing industry and human population creates pathways for the transmission of resistant bacteria, exacerbating the problem further. One Health concept, which recognizes the interconnectedness of human, animal and environmental health, enables a holistic approach to address the challenges posed by AMR. By understanding the evolution of such approach, the future of aquaculture, being the important source of a global animal protein supply, can be safeguarded. Risk mitigation strategies for AMR should be based on One Health concept to contribute to sustainable aquaculture practices that protect human and animal health, ensure food safety and protection of environment.

Porins are crucial proteins located in the outer membrane that directly influence antimicrobial resistance mechanisms and virulence in bacteria. In this study, a porin gene (Vp-porin) was cloned in V. parahaemolyticus, and the function of Vp-porin on biological characteristics and virulence was investigated. The results of sequence analysis showed that Vp-porin is highly conserved in Vibrio spp. and the predicted 3D structure showed it could form a transmembrane channel with 20 β barrel. Membrane permeabilization provides evidence that membrane integrity of ∆Vp-porin was damaged and the sensitivity to tetracycline, polymyxin B, rifampicin and cephalothin of ∆Vp-porin obvious increased. In addition, loss of Vp-porin damaged motility due to down-regulated flagellar synthesis. Besides, ∆Vp-porin exhibited attenuated cytotoxicity to Tetra-hymena. The relative survival rate of Tetrahymena infection with ∆Vp-porin was 86%, which is much high than that with WT (49%). Take together, Vp-porin in V. parahaemolyticus plays various roles in biological characteristics in membrane integrity, antimicrobial resistance and motility, and contributes to virulence.

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

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

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

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

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

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.

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

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

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.

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

Contagious pathogens have very high costs for dairy herds, and they may have zoonotic and reverse-zoonotic potentials, and may contribute in spreading antimicrobial resistance. One of the most important risk factors for spreading these infections is milking, when liner contamination may transfer the pathogens from infected to healthy cows. There is no effective protocol for avoiding the transmission of infection out of the segregation of infected cows. Recently, the availability of elastomers including patented antimicrobial components in their formulations has opened the way to explore alternative methods to decrease infection risk. Two different types of elastomers (rubber and silicon) and 9 different receipts were challenged by three major mastitis pathogens (S. aureus, S. agalactiae, and E. coli). The results showed interesting and unexpected results. Indeed, for the first time to our knowledge, we have shown that basic rubber materials have intrinsic antimicrobial activity. Silicon elastomers did not exhibit the same levels of killing activity, although they did exhibit some antibacterial capacity. Generally, a significant decrease in bacterial survival curves was observed with the tested formulations. The results observed for the various products are likely due to the specific activity of the chemical components, as well as the diverse chemical reactions that occur during their production. The availability of new tools able to reduce the risks for the spread of infections and generally decrease the bacterial load at milking, would be an important step forward to achieve a higher global sustainability of dairy production from a One Health perspective.

The use of nanoparticles as antimicrobial agents can be one of the strategies to overcome the tendency of microbes to become resistant to antibiotics’ action. In this study, two composites ZnO/Au and ZnO/Ag, having 1% wt. of noble metal content, were synthesized by simple aqueous solution methods. The structure and morphology of the resulting nanocomposites were analyzed by standard structural and optical characterization methods. The formation of Au NPs and Ag NPs in these experiments was also discussed. The antimicrobial properties of ZnO, ZnO/Au and ZnO/Ag nanomaterials were investigated against Gram-negative bacteria (Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus). The electrostatic interaction between ZnO and noble metals nanoparticles have contributed to a better visible light adsorption, which led to an enhanced antimicrobial activity. The photocatalytic tests indicated an improvement in photocatalytic degradation of the methylene blue (MB) under UV irradiation using ZnO/Au and ZnO/Ag nanocomposites compared to bare ZnO. The introduction of noble metallic nanoparticles in ZnO matrix proved to be an effective strategy to increase their antimicrobial activity against P. aeruginosa and S. aureus and their photocatalytic activity evaluated through the degradation of MB dye. Comparing the enhancing effects of Au and Ag, it was found that ZnO/Au was a better antimicrobial agent while ZnO/Ag was more effective photocatalyst under UV irradiation.

This comprehensive review examines the critical issue of antimicrobial resistance (AMR), a growing global concern with profound societal implications. This article presents an overview of the causes of AMR, including the misuse and overuse of antibiotics in healthcare, agriculture, and veterinary practices. Various conventional and advanced detection methodologies have been explored, highlighting the importance of the accurate and timely identification of resistant strains. The challenges associated with tackling AMR, encompassing scientific, economic, and regulatory aspects have been discussed in depth. In addition, this article sheds light on the far-reaching societal implications of AMR, including increased healthcare costs, treatment complexities, and potential disruptions to healthcare systems. This emphasizes the urgency of adopting proactive strategies to combat AMR and underscores the need for global cooperation, policy interventions and public awareness campaigns. By unraveling the multifaceted dimensions of AMR, this review aims to enhance our understanding, stimulate further research, and promote concerted efforts to mitigate the threat of antimicrobial resistance.

New biocements based on a powdered mixture of calcium phosphate/monetite (TTCPM) modified with the honey addition were prepared by mixing the powder and honey liquid components at a non-cytotoxic concentration of honey (up to 10% (w/v)). The setting process of the cements was not affected by the addition of honey, and the set-ting time of ~4 min corresponded to the fast setting calcium phosphate cements (CPC´s). The cement powder mixture was completely transformed into calcium-deficient nanohydroxyapatite after 24 hours of hardening in simulated body fluid, and columnar growth of long needle-like nanohydroxyapatite particles around the original calcium phosphate particles was observed in honey cements. The compressive strength of honey cements was reduced with the content of honey in the cement. The comparable antibacterial activity of cements with honey solutions was found on Escherichia coli, but very low antibacterial activity was found for Staphylococus aureus for all cements. The enhanced antioxidant inhibitory activity of composite extracts was verified. In vitro cytotoxicity testing verified the non-cytotoxic nature of honey cement extracts, and the addition of honey promoted alkaline phosphatase activity, calcium deposit production, and upregulation of osteogenic genes (osteopontin, osteocalcin, and osteonectin) by mesenchymal stem cells, demonstrating a positive synergistic effect of honey and CPC on the bioactivity of cements that could be promising therapeutic candidates for the repair of bone defects.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

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.

The non-therapeutic use of antimicrobials in poultry production contribute to the spread of drug-resistant pathogens in both birds and humans. Antibiotics are known to enhance feed effi-ciency and promote growth and weight gain of poultry. New regulatory requirements and con-sumer preferences have led to a reduced use of antibiotics in poultry production and discover natural alternatives to the antibiotic growth promoters. This interest is not just focused on the di-rect removal or inhibition of the causative microorganisms but also the prevention diseases caused by enteric pathogens using a range of feed additives. A group of promising feed additives is short- and medium-chain fatty acids and their derivatives. MCFAs possess antibacterial, anticoccidial and antiviral effects. Also, it has been proven that these acids act synergistically if they are used together with organic acids, essential oils, or probiotics. These fatty acids also benefit intestinal health integrity and homeostasis in broilers. Other effects have also been documented, including increases in intestinal angiogenesis and gene expression of tight junctions. The aim of this review is to give an overview of SCFA, MCFA as alternatives of antibiotic growth promoters and by sum-marizing the current finding in the literature, to show their possible benefits on production, meat quality and gut health in poultry.

The metal chelator PBT2 (5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline) acts as a terdentate ligand capable of forming binary and ternary Cu2+ complexes. It was clinically trialed as an Alzheimer’s disease (AD) therapeutic but failed to progress beyond phase II. The β-amyloid (Aβ) peptide associated with AD was recently concluded to form a unique Cu(Aβ) complex that is inaccessible to PBT2. Herein, it is shown that the species ascribed to this binary Cu(Aβ) complex in fact corresponds to ternary Cu(PBT2)NIm[Aβ] complexes formed by anchoring of Cu(PBT2) on imine nitrogen (NIm) donors of His side chains. The primary site of ternary complex formation is His6, having a conditional stepwise formation constant at pH 7.4 (K [M−1] ) of log K = 6.4 ± 0.1, and a second site is supplied by His13 or His14 (log K = 4.4 ± 0.1). The stability of Cu(PBT2)NIm[H13/14] is comparable with that of the simplest ternary complexes involving free imidazole (log K = 4.22 ± 0.09) and histamine (log K = 4.00 ± 0.05). The 100-fold larger formation constant for Cu(PBT2)NIm[H6] indicates that outer-sphere ligand–peptide interactions strongly stabilize its structure. Despite the relatively high stability of Cu(PBT2)NImH6, PBT2 is a promiscuous Cu2+-binding ligand capable of forming a ternary Cu(PBT2)NIm complex with any ligand containing NIm donor. These ligands include histamine, L-His, and ubiquitous His side chains of peptides and proteins in the extracellular milieu, whose combined effect should outweigh that of a single Cu(PBT2)NIm[H6] complex regardless of its stability. We therefore conclude that PBT2 is capable of accessing Cu(Aβ) complexes with high stability but not specificity. The results have implications for future AD therapeutic strategies and understanding the role of PBT2 in the bulk transport of transition metal ions. Given the repurposing of PBT2 as a drug for breaking antibiotic resistance, ternary Cu(PBT2)NIm and analogous Zn(PBT2)NIm complexes may be relevant to its antimicrobial properties.

The standard of care for nonoperative appendicitis patients involves ongoing antibiotic therapy. Yet, there is variability regarding the decision to continue outpatient parenteral antibiotic treatment (OPAT) or transition to oral (PO) antibiotics. Methods: In our single-center retrospective study, we reviewed 46 pediatric patients who underwent nonoperative management of perforated appendicitis with Interventional Radiology (IR) percutaneous drainage. We reviewed age, ethnicity, hospitalization length, antibiotic choice, route and duration, and culture data. Results. Thirty-eight [83%] patients went home on OPAT, 6[13%] on PO, and 2[4%] completed therapy while inpatient. Based on culture susceptibilities of the 38 OPAT patients, 29[76%] had oral antibiotics as an option. The three most common organisms in those sent home on OPAT included Enterococcus faecalis (38 [100%]), Bacteroides spp (33 [87%]) and Escherichia coli (27 [71%]). All patients who grew Pseudomonas aeruginosa had an oral antibiotic as a treatment option; similarly with 93% (25/27) of E. coli, 81% (13/16) of α-hemolytic Streptococcus spp, and 76% (29/38) of Enterococcus faecalis.  Conclusions:  Nearly 80% of patients sent home on OPAT had PO antibiotic regimens options based on the culture susceptibility profiles. This data indicates that using cultures and susceptibility data can help guide antibiotic management, significantly reducing PICC line placement and likely reduce healthcare costs and complications associated with central lines.

Plant diseases are among the major factors affecting plant productivity. Biological control of plant diseases is preferred over chemical control as it is environment-friendly, cost-effective, and sustainable. Among many microbes capable of providing biological control of plant diseases, probiotic Bacillus species are most promising as they can survive in adverse conditions, provide plants with a wide range of benefits including protection from phytopathogens. Wheat blast caused by Magnaporthe oryzae Triticum pathotype (MoT) has emerged as a potential threat to global wheat production. Due to unreliability of fungicides and limited cultivar resistance, we aimed to screen and identify potential antagonist bacteria collected from internal tissues of rice and wheat seeds to determine their in vitro and in vivo inhibitory effects against MoT. Dual culture and seedling assays were performed to evaluate the efficacy of probiotic bacteria. Out of 170 bacterial isolates, three bacteria (BTS-3, BTS-4, and BTLK6A) were screened as potential antagonists against MoT in vitro. Artificial inoculation at the seedling stage showed that the isolates BTS-4, BTS–3, and BTLK6A reduced 89, 88, and 85% of wheat blast disease severity, respectively, compared to mock-inoculated control. The bacterial isolates were identified as Bacillus subtilis (BTS-3) and B. velezensis (BTS-4 and BTLK6A) through genome phylogeny. The whole genome sequence of these three bacterial strains decoded a number of orthologs to intrinsic genes of antimicrobial peptides, antioxidant defense enzymes, cell wall degrading enzymes, compounds involved in the induction of systemic resistance (ISR) in host plants, and volatile compounds to make them promising biologicals to control MoT in wheat. Combined data of in vitro and in vivo along with genome analysis suggest that Bacillus spp. suppress the destructive wheat blast disease likely through antibiosis and ISR in the host plants. Further field evaluation and characterization of antimicrobial compounds are needed for a better understanding of the mode of action and practical recommendation of these bacteria for wheat blast control in the farmers’ fields.

Sepsis is a serious and life-threatening medical emergency associated with dysregulated host immune responses to infection. Like cerebral vascular or acute cardiovascular incidents, sepsis is considered a time-dependent condition having severe and long-term consequences on human health. Apart from organ support, prompt administration of appropriate antimicrobial therapy is crucial to limit the burden of complications related to sepsis in ICU patients. The management of septic patients requires comprehensive and multi-disciplinary strategies for an adequate diagnosis. Most of the ICU population receives empirical antibiotic therapy without having a confirmed diagnosis. The misuse of antibiotics in intensive care units may increase the possibility of developing multidrug resistance along with considerable ecological side effects. The first doses of empirical anti-microbial therapy are slightly higher, regardless of the presence or absence of organ dysfunction, which may upregulate the production of circulating pro-and-anti-inflammatory mediators, having negative effects on the general well-being of the patients. This notion supports the introduction of individualized antimicrobial approaches based on local patterns of resistance to ensure the appropriate dosage of empirical therapy, as well as to limit the emergence of multidrug resistance in advanced-care patients. The adequacy and treatment duration must be viewed at regular intervals for effective de-escalation, and novel diagnostic approaches must be introduced to improve the quality of care in the ICU population.

Inappropriate antimicrobial treatment can pose a risk for developing resistance against antimi-crobial drugs in bacteria. Close human contact might have a higher chance of being transmitted to humans from sheep if the sheep population is a potential reservoir of zoonotic pathogens such as shiga toxin-producing Escherichia coli (E. coli) (STEC). Therefore, this study aimed to exam-ine the sheep population in rural Bangladesh for antimicrobial resistant STEC. We screened 200 faecal samples collected from sheep in three Upazila from the Chattogram district. Phenotypical-ly positive E. coli isolates were examined for two shiga toxin-producing genes – stx1 and stx2. PCR positive STEC isolates were investigated for the presence of antimicrobial resistance genes- blaTEM, sul1 and sul2. In total, 123 of the 200 tested samples were confirmed positive E. coli by cul-tured based methods. PCR results show 17(13.8%) E. coli isolates harboured ≥ one virulent gene (stx1 or/and stx2) of STEC. Six of the tested STEC isolates exhibited blaTEM gene; eight STEC isolates had sul1 gene, and sul2 gene was detected in ten STEC isolates. To our knowledge, this study is the first to reveal a significant proportion of STEC isolated from sheep in rural Bangla-desh harbouring antimicrobial resistance genes.

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.

Abstract:Salmonella species (spp) and Escherichia coli (E. coli) are the most common infectious pathogens in poultry. Antimicrobials were given either for the treatment or growth promoters that can increase the possibility of emergence of bacterial resistance towards antimicrobials. The aim of this study was to determine the prevalence of antimicrobial resistant (AMR) Salmonella spp and E. coli isolated from a sample of broiler farms in East Coast Malaysia from 2018-2019. A total of 384 cloacal swabs were collected from broilers farms in Kelantan, Terengganu, and Pahang. The bacteria were isolated and confirmed by bacteriological and serological methods. Following that, confirmed isolates were subjected to antimicrobial susceptibility test. Salmonella spp and E. coli were recovered from the cloacal swabs samples with the overall prevalence of 6.5% and 51.8% respectively. In Kelantan, Terengganu and Pahang, the prevalence of Salmonella spp were 7%, 6.5% and 5.8% respectively, while the prevalence for E. coli were 50%, 48.3% and 58% respectively. Salmonella spp and E. coli displayed resistance towards the following antimicrobials: erythromycin (100% for both pathogens), chloramphenicol (76.2%, 84.5%), tetracycline (62%, 94.6%), ampicillin (47.7%, 87%), sulfamethoxazole/trimethoprim (42.9%, 83.3%), ciprofloxacin (4.8%, 23.8%), nalidixic acid (9.6%, 60.7%), streptomycin (19%,66%), and kanamycin (28.6%,57%), cephalotin (0%, 11%), gentamicin (0%, 20.2%) respectively. No resistance were recorded towards colistin for both pathogens. Multidrug resistance (MDR) was recorded in 82% of Salmonella spp and 100% of E. coli. These findings demonstrate the high prevalence of MDR Salmonella spp. and E. coli in broiler farms in East coast Malaysia. This could be attributed to the excessive use of antimicrobial agents by the poultry farm owners. Enhanced control measures and a strong monitoring system should be urgently implemented to reduce the emergence of antimicrobial resistance that is harmful to public health.

For screening excellent lactic acid bacteria (LAB) strains to inhibit Escherichia (E.) coli (ETEC) K88, inhibitory activities of more than 1100 LAB strains isolated from different materials and kept in the lab were evaluated in this study. Nine strains with inhibition zone at least 22.00 mm (including that of hole puncher 10.00 mm) and good physiological and biochemical characteristics identified by 16S DNA gene sequencing and recA gene multiple detection, were assigned to Lactobacillus (L.) plantarum subsp. plantarum (5), L. fermentum (1), L. reuteri (1), W. cibaria (1) and E. faecalis (1), respectively. As investigated for their tolerance abilities and safety, only strain ZA3 possessed high hydrophobicity and auto-aggregation abilities, had high survival rate in low pH, bile salt environment and GI fluids, sensitive to ampicillin, resistant to norfloxacin and amikacin, without hemolytic activity and didn’t carry antibiotic resistance genes, exhibited broad spectrum activity against a wide range of microorganisms, and antibacterial substance may attribute to organic acids, especially lactic acid and acetic acid. The results indicated that the selected strain L. plantarum subsp. plantarum ZA3 could be considered a potential probiotic to inhibit ETEC K88 for further research.

With the increasing use of genome sequencing as a surveillance tool for molecular epidemiology of antimicrobial resistance (AMR), databases and clear nomenclature for AMR gene families are critical. Due to the convoluted nomenclatural history of the integron-associated trimethoprim-resistant dihydrofolatereductase (dfr) gene family, we decided to conduct a literature review, comparative sequence analysis, and phylogenetic investigation of the dfr family, the results of which are presented here and available at the Comprehensive Antibiotic Resistance Database (CARD). Overall, literature review and phylogenetic analysis resolved gene name synonyms based on sequence. We recommend adoption of phylogenetic methods to help guide AMR gene naming efforts and relegation of misleading names to synonyms.

Cinnamaldehyde, a natural preservative that can non-specifically deactivate foodborne pathogens, was successfully incorporated into fish skin gelatin (FSG) solutions and blow spun into uniform nanofibers. The effects of cinnamaldehyde ratios (5-30%, w/w FSG) on physicochemical properties of fiber-forming emulsions (FFEs) and their nanofibers were investigated. Higher ratios resulted in higher values in particle size and viscosity of FFEs, as well as higher values in diameter of nanofibers. Loss of cinnamaldehyde was observed during solution blow spinning (SBS) process and cinnamaldehyde was mainly located on the surface of resultant nanofibers. Nanofibers all showed antibacterial activity by direct diffusion and vapor release against Escherichia coli O157:H7, Salmonella typhimurium, and Listeria monocytogenes. Inhibition zones increased as cinnamaldehyde ratio increased. Nanofibers showed larger inhibition effects than films prepared by casting method when S. typhimurium was exposed to the released cinnamaldehyde vapor, although films had higher remaining cinnamaldehyde than nanofibers after preparation. Lower temperature was favorable for cinnamaldehyde retention, and nanofibers added with 10% cinnamaldehyde ratio showed the highest retention over eight-weeks of storage. Results suggest that FSG nanofibers can be prepared by SBS as carriers for antimicrobials.

This study developed gelatin-based films with incorporation of microcrystalline cellulose as reinforcement material. Clove (Syzygium aromaticum), nutmeg (Myristica fragrans), and black pepper (Piper nigrum) oleoresins containing antimicrobial compounds of natural origin were incorporated into films. The mechanical, thermal, optical, and structural properties, as well as color, resistance to sealing and permeability to water vapor, light, and oil of the films were determined. Adding oleoresins to the gelatin matrix increased elongation of the material and significantly diminished its permeability to water vapor and oil. Evaluation of the potential use of films containing different oleoresins as bread packaging material was influenced by the film properties. The biocomposite film containing oleoresin from black pepper was the most effective packaging material for maintaining the bread’s quality characteristics.

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

Phytophthora-induced crop diseases, commonly known as “plant plagues,” pose a significant threat to global food security. In this study, strain ASG80 was isolated from sisal roots and demonstrated broad-spectrum antagonistic activity against several Phytophthora species and fungal pathogens. Strain ASG80 was identified as Streptomyces luteireticuli via phylogenetic analysis, digital DNA-DNA hybridization (dDDH), and average nucleotide identity (ANI). Whole-genome sequencing identified 40 biosynthetic gene clusters (BGCs) related to secondary metabolite production, including antimicrobial compounds. Strain ASG80 extract exhibited broad-spectrum inhibitory activity against Phytophthora nicotianae, P. vignae, P. cinnamomi, and P. sojae. Pot experiments showed that strain ASG80 extract significantly reduced sisal zebra disease incidence, with efficacy comparable to the fungicide metalaxyl. These findings suggest that strain ASG80 is a promising biocontrol agent with substantial potential for managing Phytophthora-related diseases in agriculture.

The discovery of antibiotics was one of the greatest achievements in human history, however, antibiotic resistance evolved no later than the introduction of antibiotics. The rapid evolution of antibiotic-resistant pathogens soon became a nightmare and remained a global healthcare threat. There is an urgent need to have new alternatives or new strategies to combat the multi-drug resistant superbugs such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), extended-spectrum β-lactamases (ESBL) bearing multidrug-resistant Acinetobacter baumannii (MDR-AB), Escherichia coli, and Klebsiella pneumonia. Antimicrobial peptides (AMPs) have been considered promising agents equipped with unique mechanisms of action along with several other benefits to fight the battle against drug-resistant superbugs. Overall, the current review summarizes the mechanisms of drug-resistant development, the mechanism of action adopted by AMPs to combat drug-resistant pathogens, and the immunomodulatory properties of AMPs. Additionally, we have also reviewed the synergistic potential of AMPs with conventional antibiotics and the associated challenges and limitations of AMPs in the way of pharmacological development for therapeutic applications in clinical settings.

Almost fifty years after the introduction of antibiotics as an antimicrobial agent, we are facing an increasing number of multi-resistant microbials. The search for new antimicrobial compounds emerged as a promising alternative to treatments for diseases caused by microorganisms such as fungi and bacteria. Thus, endophytic fungi are gaining recognition for their varied metabolites that may possess antimicrobial properties. In our research, we isolated, from Calea pinnatifida, six endophytic fungi identified as Colletotrichum siamense, Colletotrichum karstii, Hypomontagnella barbarensis, Neopestalotiopsis clavispora, Nigrospora sacchari-officinarum and Annulohypoxylon moriforme. Analyses of microbial secondary metabolites by utilizing UHPLC-HR-ESI-MS/MS in conjunction with molecular networking, allowed the annotation of 9 compounds, 5 of them from GNPS spectral library match, and 4 from prediction-based on the molecular network, and allowed the isolation of two pairs of Acyl-tetronic acid derivatives distereoisomeric identified by NMR spectrum. In this sense, the present study underlines the value of endophytic fungi as a reservoir of potentially new antimicrobial agents.

The rise of antibiotic-resistant pathogens represents a significant global challenge in infectious disease control, which is amplified by the decline in the discovery of novel antibiotics. Staphylococcus aureus continues to be a highly significant pathogen causing infections in multiple organs and tissues in both healthcare institutions and community settings. The bacterium has become increasingly resistant to all available antibiotics. Consequently, there is an urgent need for novel small molecules that inhibit growth or impair survival of bacterial pathogens. Given their large structural and chemical diversity as well as often unique mechanisms of action, natural products represent an excellent avenue for the discovery and development of novel antimicrobial treatments. Anaephene A and B are two such naturally occurring compounds with significant antimicrobial activity against gram-positive bacteria. Here, we report the rapid syntheses and biological characterization of five novel anaephene derivatives, which display low cytotoxicity against mammalian cells but potent antibacterial activity against various S. aureus strains, including methicillin resistant S. aureus (MRSA) and the multi drug-resistant community acquired strain USA300LAC. A Sonogashira cross-coupling reaction served as the key step for the synthesis of the alkyl pyridinol products. Using the compound JC-01-074, which displays bactericidal activity already at low concentrations (MIC: 16 mg/ml), we provide evidence that alkyl pyridinols target actively growing and biofilm-forming cells and show that these compounds cause disruption and deformation of the staphylococcal membrane, indicating a membrane associated mechanism of action.

Metals play vital roles in biological systems, with iron/heme being essential for cellular and metabolic functions necessary for survival and/or virulence in many bacterial pathogens. Given the rise of bacterial resistance to current antibiotics, there is an urgent need for the development of non-toxic and novel antibiotics that do not contribute to resistance to other antibiotics. Gallium, which mimics iron, has emerged as a promising antimicrobial agent, offering a novel approach to combat bacterial infections. Gallium does not have any known functions in biological systems. Gallium exerts its effects primarily by replacing iron in redox enzymes, effectively inhibiting bacterial growth by targeting multiple iron/heme-dependent biological processes and suppressing the development of drug resistance. The aim of this review is to highlight recent findings on the mechanisms of action of gallium and provide further insights into the development of gallium-based compounds. Understanding the mechanisms underlying gallium’s biological activities will enhance its therapeutic application across various medical fields, offering promising avenues for the treatment of infectious diseases, cancer, and inflammatory conditions.

The exponential rise of bacterial resistance poses a threat to antibiotic efficacy, with a great impact on public health. This study aims to analyze the correlation between antibiotic consumption and the emergence of bacterial resistance. Conducted retrospectively at Charles Nicolle Hospital in Tunis, Tunisia from 2010 to 2022, this study was based on STKMED® software for antibiotic consumption data, hospital administrative records for the number of hospitalization days, and SIRSCAN® software for bacteriological data. Data processing was performed using Excel® software, and analysis was conducted using SPSS23®. In 2022, Consumption was almost evenly split between the two major “AWaRe” groups, with 49.33% for "Access" and 46.89% for "Watch", and the consumption of the "Reserve" group also increased, accounting for 3.77% of the total. Bacterial resistances, notably carbapenem-resistant Klebsiella pneumoniae, increased. Seventy-four significant correlations were identified, including those be-tween carbapenem consumption and resistance in Escherichia coli and Klebsiella pneumoniae strains. However, no significant corre-lation was observed with imipenem-resistant Pseudomonas aeruginosa strains. The significant correlations between the emergence of bacterial resistance and antibiotic use, particularly with antibiotics in the "Watch" and "Reserve" groups, underscore the urgent need to continue efforts to combat this threat through rational antibiotic use.

Tuberculosis (TB) remains a global public health issue, particularly in developing countries. Hematopoietic stem cell transplant (HSCT) recipients are at elevated risk for TB due to immunosuppression. This retrospective study (2005-2022) assessed a preemptive latent tuberculosis infection (LTBI) screening and treatment strategy in 338 HSCT recipients and their donors. Screening included tuberculin skin test (TST) or QuantiFERON-TB Gold (QFT), and pulmonary imaging, with positive cases receiving isoniazid (INH) therapy. Statistical analyses aimed to compare TB reactivation rates, overall survival (OS), and relapse-free survival (RFS) across HSCT groups. Of 338 patients, 92 (27%) were diagnosed with LTBI. Screening involved TST in 325 cases and QFT in 13. INH therapy was completed by 81 patients, with 5 discontinuing due to hepatotoxicity. The cumulative incidence of active TB was 0.6%, and LTBI reactivation rate in patients who received INH was 1.2%. LTBI status did not affect OS or RFS. Our study exemplifies the effectiveness of LTBI protocols incorporating TST/QFT and CT-scan testing, followed by INH therapy, in reducing TB reactivation among HSCT recipients in a high-burden region.

A novel electrospun nanofiber was developed using polyamide-6 (PA) and ε-poly-L-lysine (PL). PA is a popular textile polymer having desirable mechanical and thermal properties, chemical stability, and biocompatibility. However, PA nanofibers are prone to bacterial growth and user discomfort. PL, a natural homopolyamide, is non-toxic, antimicrobial, and hydrophilic but lacks spinnability due to its low molecular weight. Given its similar backbone structure as PA, with an additional amino side chain, PL was integrated with PA to develop multifunctional nanofibers. This study explores a simple, scalable method to obtain PL nanofibers by utilizing the structurally similar PA as the base. The goal was to enhance the functionality of PA by addressing its drawbacks. The study demonstrates spinnability of varying concentrations of PL with base PA while exploring compositions with higher PL concentrations than previously reported. Electrospinning parameters were studied to optimize the nanofiber properties. The effects of PL addition on morphology, hydrophilicity, thermal stability, mechanical performance, and long-term antimicrobial activity of nanofibers were evaluated. The inclusion of PL in PA-based nanofibers resulted in super hydrophilicity, increased tensile strength, and efficient antimicrobial properties with long-term stability. These enhanced characteristics hold promise for the composite nanofiber’s application in medical and protective textiles.

Antimicrobial resistance (AMR) is a major public health threat linked to increased morbidity and mortality. It has the potential to return us to the pre-antibiotic era. Antimicrobial stewardship (AMS) programs are recognized as a key intervention to improve antimicrobial use and combat AMR. However, implementation of AMS programs remains limited in Africa, particularly in Rwanda. This qualitative study, conducted at King Faisal Hospital (KFH) in Rwanda, aimed at assessing current prescription practices to identify areas for improvement and promote adherence to AMS principles. The interviews were recorded, transcribed, and thematically analyzed, revealing four emerging themes. First, emerged on AMS activities that were working well which includes availability of microbiology laboratory results, and prescription guidelines as factors influencing antibiotic prescription adjustments. Second, Implementations challenges to AMS which identified the prescription of broad-spectrum antibiotics, limited local data on AMR patterns, stock-outs of essential antibiotics, Thirdly, the importance of adhering to AMR management guidelines at KFH was underscored. Lastly, participant recommendations centered on regular training for healthcare workers, widespread dissemination of AMR findings across departments, and the enforcement of antibiotic restriction policies. These actions can improve prescription behaviors, upholding the highest standards of patient care, and strengthening the nascent AMS program.

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

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

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

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

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

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.

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

Excessive use of antibiotics to control colibacillosis on poultry farms in Morocco contributes to the development of multiresistant avian pathogenic E. coli. Autogenous vaccines are an alternative to antibiotic usage; the main goal of this study was to assess the efficacy of this approach to control recurrent outbreaks of colibacillosis in a large broiler production flow. A tetravalent autogenous vaccine (serotypes O78, O88, O91, and O185) was produced from E. coli strains isolated from clinical lesions in breeding hens and used on two farms (65,000 breeding hens in total). On each farm, contemporaneous groups were included: groups vaccinated twice (12 and 18 weeks of age) and unvaccinated control groups. The performances of these flocks, as well as the performances of broilers hatched from these breeders (12 farms, over 600,000 broilers in total), were recorded. A significant reduction in lesion scores, mortality rate and a significant increase in the number of saleable day-old chicks were observed among vaccinated hens. In broilers, body weight at slaughter, lesion scores, food conversion ratio, mortality and condemnation rates were significantly improved. This is the first field observation of a lasting effect of breeder hens immunization with an autogenous vaccine against E. coli on their offspring.

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.

Sporothrix brasiliensis is the most pathogenic species, responsible for the Brazilian cat-transmitted sporotrichosis hyperendemics. In this scenario, investigation of pathogen-host interaction can provide relevant information for future treatment strategies. To this end, the invertebrate Galleria mellonella has proven to be a suitable alternative to evaluate the virulence of pathogenic fungi since the insect immune system is similar to the mammalian innate immune response. The aim of this work was to investigate phenotypic and molecular aspects of the immune response of G. mellonella throughout the S. brasiliensis infection. Hemocyte density and the evolution of the fungal load were evaluated. In parallel, RT- qPCR expression analysis of genes encoding antimicrobial peptides (Gallerimycin and Galiomycin) and stress management genes (C7 Contig 15362 and C8 Contig 1910) was conducted. Fungal load and hemocyte densities were proportionally increasing simultaneously to the deleterious morphological events and larvae mortality. Gallerimycin, C7 Contig 15362, and C8 Contig 19101 genes were positively regulated (p&lt;0.05) at distinct moments of S. brasiliensis infection, characterizing a time-dependent and alternately modulated profile. Galiomycin gene expression remained unchanged. Our results contribute to the future proposal of potential alternative pathways to treat and, consequently, control S. brasiliensis zoonosis, a major public Health in Latin America.