Emergence Of Antimicrobial Resistance Research Articles

Multi-Faceted Antimicrobial Efficacy of a Quinoline-Derived Bidentate Copper(II) Ligand Complex and Its Hydrogel Encapsulated Formulation in Methicillin-Resistant Staphylococcus aureus Inhibition and Wound Management.

The emergence of antimicrobial resistance, exemplified by methicillin-resistant Staphylococcus aureus (MRSA), poses a grave threat to public health globally. Over time, MRSA has evolved resistance to multiple antibiotics, challenging conventional treatment strategies. The relentless adaptability of MRSA underscores the urgent need for innovative and targeted antimicrobial approaches to combat this resilient pathogen. Ancient knowledge and practices, along with scientific evidence, have established that metallic copper, and its organic coordination complexes can act as potential antibacterial substances. In search of a smart and effective antimicrobial against MRSA, we designed, synthesized, and characterized a bidentate copper(II) ligand complex (SG-Cu) utilizing a comprehensive array of analytical techniques, including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and others. Antibacterial efficacy and mechanism of action of the complex were assessed through bacterial growth analyses, bacterial membrane perturbation assays, ROS elicitation assays, and field emission scanning electron microscopy. SG-Cu was found to maintain robust biocompatibility against the mammalian cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated significant biofilm disruptive tendency evidenced by the retardation of sliding motility, reduction in slime production, reduction in biofilm viability, and enhanced biofilm eradication, both in vitro and in urinary catheters. In vivo studies on murine excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release of SG-Cu from the gel matrix, facilitating accelerated wound healing and effective wound disinfection. This multifaceted investigation highlights the potential of SG-Cu as a versatile option for combating MRSA infections and promoting wound healing, solidifying its claim to be developed into a viable therapeutic.

The dark side of drug repurposing. From clinical trial challenges to antimicrobial resistance: analysis based on three major fields

Drug repurposing is a strategic endeavor that entails the identification of novel therapeutic applications for pharmaceuticals that are already available in the market. Despite the advantageous nature of implementing this particular strategy owing to its cost-effectiveness and efficiency in reducing the time required for the drug discovery process, it is essential to bear in mind that there are various factors that must be meticulously considered and taken into account. Up to this point, there has been a noticeable absence of comprehensive analyses that shed light on the limitations of repurposing drugs. The primary aim of this review is to conduct a thorough illustration of the various challenges that arise when contemplating drug repurposing from a clinical perspective in three major fields—cardiovascular, cancer, and diabetes—and to further underscore the potential risks associated with the emergence of antimicrobial resistance (AMR) when employing repurposed antibiotics for the treatment of noninfectious and infectious diseases. The process of developing repurposed medications necessitates the application of creativity and innovation in designing the development program, as the body of evidence may differ for each specific case. In order to effectively repurpose drugs, it is crucial to consider the clinical implications and potential drawbacks that may arise during this process. By comprehensively analyzing these challenges, we can attain a deeper comprehension of the intricacies involved in drug repurposing, which will ultimately lead to the development of more efficacious and safe therapeutic approaches.

Antibiotic resistance profiles of sentinel bacteria isolated from aquaculture in Cambodia

ABSTRACT The misuse of antibiotics and the emergence of antimicrobial resistance (AMR) is a concern in the aquaculture industry because it contributes to global health risks and impacts the environment. This study analyzed the AMR of sentinel bacteria associated with striped catfish (Pangasianodon hypophthalmus) and giant snakehead (Channa micropeltes), the two main fish species reared in the pond culture in Cambodia. Phenotypic and genotypic characterization of the recovered isolates from fish, water, and sediment revealed the presence of bacteria, such as 22 species belonging to families Aeromonadaceae, Enterobacteriaceae, and Pseudomonadaceae. Among 48 isolates, Aeromonas caviae (n = 2), Aeromonas hydrophila (n = 2), Aeromonas ichthiosmia (n = 1), and Aeromonas salmonicida (n = 4) were detected. Both A. salmonicida and A. hydrophila are known as fish pathogens that occur worldwide in both fresh and marine water aquaculture. Antibiotic susceptibility testing for Enterobacteriaceae and Pseudomonadaceae species and six antibiotics for Aeromonadaceae species revealed antibiotic resistance patterns of 24 (50%) isolates among the 48 isolates with higher multiple antibiotic resistance index scores (>0.2). All the isolates of Enterobacteriaceae were susceptible to ciprofloxacin. Ciprofloxacin is a frontline antibiotic that is not recommended for use in aquaculture. This study expands our knowledge of the AMR status in aquaculture farms, which is very limited in Cambodia.

Dermatophytosis in domestic cats: Identification, and treatment in an Indian context

The surge in domestic cat adoption across India, particularly the rising preference for high-pedigree cats, coupled with environmental factors, has resulted in increased incidence of dermatophytosis among feline companions. Despite this growing concern, there is a noticeable scarcity of studies in India delving into the etiological factors contributing to dermatophytosis in cats. This disease is a threat to animal health and carries public health significance, given that cats are recognized reservoir hosts for Microsporum canis, a common dermatophyte affecting humans and animals. This study endeavours to identify the dermatophytes affecting cats and establish a standardized therapeutic regimen while accounting for the local stigma surrounding the regular bathing of cats. The study involved the examination of 82 cats presenting dermatological lesions, when subjected to cultural examination in dermatophyte test medium revealed 36 afflicted with dermatophytes. Isolates were presumptively identified by staining using lactophenol cotton blue, Chicago sky blue 6B, and Calcofluor white stains. Molecular-level identification of the isolates was confirmed through PCR-RFLP, amplifying the Internal Transcribed Spacer Sequence of 16 s rDNA, followed by restriction digestion using the Mva1 enzyme. Among the thirty-six isolates, 29 were identified as M. canis, while the remaining 7 were M. gypseum. The cases were categorized into five groups and treated with Lime Sulphur dip, 4 % chlorhexidine shampoo, a shampoo containing 2 % miconazole and 4 % chlorhexidine, oral itraconazole alone, and a combination of oral itraconazole with lime-Sulphur dip. Statistical analysis revealed that the response was notably swifter with lime Sulphur dip when considering only topical therapy. Moreover, the mycological cure was most expeditious when combining Lime Sulphur dip with oral itraconazole. These findings underscore the pivotal role of topical biocides in feline dermatophytosis treatment, potentially reducing the reliance on specific antifungals and thereby contributing to the mitigation of antimicrobial resistance emergence.

Discovery of Leaderless Bacteriocins through Genome Mining

The emergence of antimicrobial resistance has prompted the search for antibiotic alternatives, and bacteriocins have emerged as promising alternatives to traditional antibiotics. Bacteriocins refers to a large family of antimicrobial peptides that are ribosomally synthesized by bacteria. The class of bacteriocins called leaderless bacteriocins is a unique group distinguished by the absence of a leader peptide and post-translational modifications, and hence their linear structures. Members of this class have been discovered by a traditional approach of screening bacterial isolates for antimicrobial activity and subsequently identifying the active molecule. This study presents the first extensive genome mining approach for leaderless bacteriocin discovery. In detail, we performed a precursor peptide-based genome mining to search for novel leaderless bacteriocins. Over 400 producer organisms with putative leaderless bacteriocins encoded in their genomes were identified, revealing the widespread occurrence of leaderless bacteriocins. Among the identified putative bacteriocins, 122 are unique peptide sequences. To validate our genome mining results, a novel bacteriocin we termed miticin, encoded in the genome of Streptococcus mitis, was obtained through chemical synthesis. Miticin was indeed found to be active, specifically against a wide range of Gram-positive bacteria. With this study, we provide the foundation for exploring a repertoire of potential novel antimicrobials identified through an innovative bioinformatics-guided approach, representing a significant leap compared to traditional screening and isolation methods for the discovery of bioactive molecules, specifically leaderless bacteriocins.

An In Vitro Study to Evaluate the Synergy of Baptisia tinctoria against Salmonella typhi

AbstractAs a consequence of gradual emergence of anti-microbial resistance, the anti-biogram profile of the microbe Salmonella typhi has undergone substantial changes. Patients frequently utilise homeopathy for the flu season and other serious illnesses. Although the use of Baptisia tinctoria (BT) is extensively described in homeopathic literature and in phytomedicine, scientific exploration has never been done. In this study, we have made an effort to understand the anti-typhoidal effect of BT at different concentrations. S. typhi (ATCC 6539) from a freshly prepared stock culture was used in this experiment. We also procured an international strain of Escherichia coli (ATCC 25922 strain) which was taken as control. The antibiotic susceptibility patterns of the isolates were determined by the Kirby-Bauer disc diffusion method according to the Clinical and Laboratory Standards Institute guidelines and interpretative criteria (National Committee for Clinical Laboratory Standards 2000) using antibiotic discs (Hi Media Laboratory. Pvt. Ltd., Mumbai, Maharashtra, India), namely cefotaxime (30 μg), ceftazidime (30 μg), ciprofloxacin (5 μg), tetracycline (30 μg), chloramphenicol (30 μg), streptomycin (10 μg), ampicillin (10 μg), gentamicin (10 μg), kanamycin (30 μg), nalidixic acid (30 μg) and trimethoprim (5 μg). BT in its 6CH potency showed the greatest growth inhibition zone, not just amidst the homeopathic potency gradient. It has shown the highest growth inhibition zone of 28mm, more than any conventional antibiotic. Ethanolic extract of BT can be considered to combat against array of infections caused by S. typhi species alongside that it can also be considered as adjuvant with conventional antibiotics for better result.

From Gene Editing to Biofilm Busting: CRISPR-CAS9 Against Antibiotic Resistance-A Review.

In recent decades, the development of novel antimicrobials has significantly slowed due to the emergence of antimicrobial resistance (AMR), intensifying the global struggle against infectious diseases. Microbial populations worldwide rapidly develop resistance due to the widespread use of antibiotics, primarily targeting drug-resistant germs. A prominent manifestation of this resistance is the formation of biofilms, where bacteria create protective layers using signaling pathways such as quorum sensing. In response to this challenge, the CRISPR-Cas9 method has emerged as a ground-breaking strategy to counter biofilms. Initially identified as the "adaptive immune system" of bacteria, CRISPR-Cas9 has evolved into a state-of-the-art genetic engineering tool. Its exceptional precision in altering specific genes across diverse microorganisms positions it as a promising alternative for addressing antibiotic resistance by selectively modifying genes in diverse microorganisms. This comprehensive review concentrates on the historical background, discovery, developmental stages, and distinct components of CRISPR Cas9 technology. Emphasizing its role as a widely used genome engineering tool, the review explores how CRISPR Cas9 can significantly contribute to the targeted disruption of genes responsible for biofilm formation, highlighting its pivotal role in reshaping strategies to combat antibiotic resistance and mitigate the challenges posed by biofilm-associated infectious diseases.

Gut microbiome and resistome characterization of pigs treated with commonly used post-weaning diarrhea treatments

BackgroundThe global burden of antimicrobial resistance demands additional measures to ensure the sustainable and conscious use of antimicrobials. For the swine industry, the post-weaning period is critical and for many years, antimicrobials have been the most effective strategy to control and treat post-weaning related infections. Among them, post-weaning diarrhea causes vast economic losses, as it severely compromises piglets’ health and growth performance. In this study, 210 piglets were transferred from a farm with recurrent cases of post-weaning diarrhea to an experimental farm and divided into six different treatment groups to determine the effect of the different treatments on the growth performance and survival, the microbiome, and the resistome in a cross-sectional and longitudinal study. The different treatments included antimicrobials trimethoprim/sulfamethoxazole, colistin, and gentamicin, an oral commercial vaccine, a control with water acidification, and an untreated control. An extra group remained at the farm of origin following the implemented amoxicillin routine treatment. A total of 280 fecal samples from pigs at four different sampling times were selected for metagenomics: before weaning-treatment at the farm of origin, and three days, two weeks, and four weeks post-treatment.ResultsThe control group with water acidification showed a reduced death risk in the survival analyses and non-significant differences in average daily weight gain in comparison to the antibiotic-treated groups. However, the growth-promoting effect among antibiotic-treated groups was demonstrated when comparing against the untreated control group at the experimental farm. After four weeks of treatment, diversity indexes revealed significantly decreased diversity for the untreated control and the group that remained at the farm of origin treated with amoxicillin. For this last group, impaired microbial diversity could be related to the continuous amoxicillin treatment carried out at the farm. Analysis of the resistome showed that both gentamicin and amoxicillin treatments significantly contributed to the emergence of resistance, while trimethoprim/sulphonamide and colistin did not, suggesting that different treatments contribute differently to the emergence of resistance.ConclusionsOverall, this shotgun longitudinal metagenomics analysis demonstrates that non-antibiotic alternatives, such as water acidification, can contribute to reducing the emergence of antimicrobial resistance without compromising pig growth performance and gut microbiome.

Understanding the awareness of antimicrobial resistance amongst commercial poultry farmers in northwestern Nigeria

The emergence of antimicrobial resistance (AMR) in both humans and animals is a growing health threat worldwide. Significant quantities of antibiotics are used in the livestock production sector, particularly in poultry farming to enhance growth and productivity. A cross-sectional study was conducted in three states of northwestern Nigeria to understand the level of knowledge, attitude, and practice of commercial poultry farmers on antimicrobial resistance. A total of 247 poultry farmers enrolled in the study comprising 100 (40.5%) from Sokoto, 68 from Kebbi (27.5%) and 79 (32.0%) from Zamfara States. A significant number of the farmers have good knowledge of antimicrobial use (94.74%), and the potential emergence of antimicrobial resistant bacteria due to irrational administration of antibiotics (83.0%). Kruskal-Wallis test showed a significant difference in farmers’ knowledge of AMR based on their educational qualification (p<0.001) as farmers with bachelor’s degree (BSc) being more knowledgeable than those with Ordinary National Diploma (OND) and those who only completed primary or secondary education. A statistically significant difference was also observed in the attitude of the participants based on State (p<0.001) and educational qualification (p=0.013). The study provided valuable insight into the understanding of antimicrobial resistance amongst commercial poultry farmers in the region. The findings necessitate the need for educational interventions and initiatives through enlightenment campaigns and deployment of extension workers to reach farmers with low level of education to further improve their attitudes and practice towards responsible use of antibiotics.

Bacteriophage therapy in musculoskeletal infections: from basic science to clinical application.

The treatment of musculoskeletal infections (MSIs), including periprosthetic joint infection (PJI) and fracture-related infection (FRI), is often complicated by biofilm-related challenges necessitating multiple revision surgeries and incurring substantial costs. The emergence of antimicrobial resistance (AMR) adds to the complexity of the problem, leading to increased morbidity and healthcare expenses. There is an urgent need for novel antibacterial strategies, with the World Health Organization endorsing non-traditional approaches like bacteriophage (phage) therapy. Phage therapy, involving the targeted application of lytic potent phages, shows promise in the treatment of MSIs. Although historical clinical trials and recent case studies present significant milestones in the evolution of phage therapy over the past century, challenges persist, including variability in study designs, administration protocols and phage selection. Efforts to enhance treatment efficacy consist of personalized phage therapy and combination with antibiotics. Future perspectives entail addressing regulatory barriers, standardizing treatment protocols, and conducting high-quality clinical trials to establish phage therapy's efficacy for the treatment of MSIs. Initiatives like the PHAGEFORCE study and the PHAGEinLYON Clinic programme aim to streamline phage therapy, facilitating personalized treatment approaches and systematic data collection to advance its clinical utility in these challenging infections.

Knowledge, Attitudes, Practices, and Risk Perception of Antimicrobial Use and Antimicrobial Resistance Among Dairy Farm Owners/Workers in Addis Ababa, Ethiopia.

Antimicrobial resistance (AMR) is one of the most significant global health threats to the public, animals, and the ecosystem. Inappropriate use of antibiotics in food animals is considered a major driver of AMR in humans. This study was conducted to assess the knowledge, attitude, practices, and risk perception (KAPP) of dairy farm owners/workers in Addis Ababa about antibiotic use and resistance. A face-to-face interview using a structured questionnaire was conducted with 281 respondents in four selected subcities of Addis Ababa. The responses provided by each participant were recoded into a binary scale based on the mean score of each domain. Pearson chi-square was used to check the association between the KAPP and sociodemographic characteristics of the respondents and logistic regression analysis was done to explore the factors associated with KAPP. Overall, more than half of the surveyed dairy farm owners/workers had good knowledge (57.7%) and appropriate practice (53.0%), while less than half of the respondents showed desirable attitudes (47.7%) and positive risk perceptions (42.7%). The findings revealed a strong association between the respondents' KAPP and education and between knowledge and risk perception and farming experience. This study found that continuous education of dairy farm owners/workers regarding antimicrobial usage and antimicrobial resistance in dairy farms will increase their awareness and perception of risk as well as motivate them to adopt desirable attitudes and appropriate practices, and consequently limit inappropriate use of antimicrobials leading to mitigating emergence of AMR.

Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance.

The ecological and evolutionary mechanisms of antimicrobial resistance (AMR) emergence within patients and how these vary across bacterial infections are poorly understood. Increasingly widespread use of pathogen genome sequencing in the clinic enables a deeper understanding of these processes. In this Review, we explore the clinical evidence to support four major mechanisms of within-patient AMR emergence in bacteria: spontaneous resistance mutations; in situ horizontal gene transfer of resistance genes; selection of pre-existing resistance; and immigration of resistant lineages. Within-patient AMR emergence occurs across a wide range of host niches and bacterial species, but the importance of each mechanism varies between bacterial species and infection sites within the body. We identify potential drivers of such differences and discuss how ecological and evolutionary analysis could be embedded within clinical trials of antimicrobials, which are powerful but underused tools for understanding why these mechanisms vary between pathogens, infections and individuals. Ultimately, improving understanding of how host niche, bacterial species and antibiotic mode of action combine to govern the ecological and evolutionary mechanism of AMR emergence in patients will enable more predictive and personalized diagnosis and antimicrobial therapies.

A novel variant in Salmonella genomic island 1 of multidrug-resistant Salmonella enterica serovar Kentucky ST198.

Salmonella enterica serovar Kentucky ST198 is a major health threat due to its resistance to ciprofloxacin and several other drugs, including third-generation cephalosporins. Many drug-resistant genes have been identified in the Salmonella genomic island 1 variant K (SGI1-K). In this study, we investigated the antimicrobial resistance (AMR) profile and genotypic relatedness of two isolates of ciprofloxacin-resistant (CIPR) S. Kentucky ST198 from poultry in Northeastern Thailand. We successfully assembled the complete genomes of both isolates, namely SSSE-01 and SSSE-03, using hybrid de novo assembly of both short- and long-read sequence data. The complete genomes revealed their highly similar genomic structures and a novel variant of SGI1-K underlying multidrug-resistant (MDR) patterns, including the presence of blaTEM-1b, which confers resistance to beta-lactams, including cephalosporins and lnu(F) which confers resistance to lincomycin and other lincosamides. In addition, the chromosomal mutations in the quinolone resistance-determining region (QRDR) were found at positions 83 (Ser83Phe) and 87 (Asp87Asn) of GyrA and at positions 57 (Thr57Ser) and 80 (Ser80Ile) of ParC suggesting high resistance to ciprofloxacin. We also compared SSSE-01 and SSSE-03 with publicly available complete genome data and revealed significant variations in SGI1-K genetic structures and variable relationships to antibiotic resistance. In comparison to the other isolates, SGI1-K of SSSE-01 and SSSE-03 had a relatively large deletion in the backbone, spanning from S011 (traG∆) to S027 (resG), and the inversion of the IS26-S044∆-yidY segment. Their MDR region was characterized by the inversion of a large segment, including the mer operon and the relocation of IntI1 and several resistance genes downstream of the IS26-S044∆-yidY segment. These structural changes were likely mediated by the recombination of IS26. The findings broaden our understanding of the possible evolution pathway of SGI1-K in fostering drug resistance, which may provide opportunities to control these MDR strains.IMPORTANCEThe emergence of ciprofloxacin-resistant (CIPR) Salmonella Kentucky ST198 globally has raised significant concerns. This study focuses on two poultry isolates from Thailand, revealing a distinct Salmonella genomic island 1 variant K (SGI1-K) genetic structure. Remarkably, multiple antibiotic resistance genes (ARGs) were identified within the SGI1-K as well as other locations in the chromosome, but not in plasmids. Comparing the SGI1-K genetic structures among global and even within-country isolates unveiled substantial variations. Intriguingly, certain isolates lacked ARGs within the SGI1-K, while others had ARGs relocated outside. The presence of chromosomal extended-spectrum β-lactamase (ESBL) genes and lincosamide resistance, lnu(F), gene, could potentially inform the choices of the treatment of CIPRS. Kentucky ST198 infections in humans. This study highlights the importance of understanding the diverse genetic structures of SGI1-K and emphasizes the role of animals and humans in the emergence of antimicrobial resistance.

Actionable mechanisms of drug tolerance and resistance in Mycobacterium tuberculosis.

The emergence of antimicrobial resistance (AMR) across bacterial pathogens presents a serious threat to global health. This threat is further exacerbated in tuberculosis (TB), mainly due to a protracted treatment regimen involving a combination of drugs. A diversity of factors contributes to the emergence of drug resistance in TB, which is caused by the pathogen Mycobacterium tuberculosis (Mtb). While the traditional genetic mutation-driven drug resistance mechanisms operate in Mtb, there are also several additional unique features of drug resistance in this pathogen. Research in the past decade has enriched our understanding of such unconventional factors as efflux pumps, bacterial heterogeneity, metabolic states, and host microenvironment. Given that the discovery of new antibiotics is outpaced by the emergence of drug resistance patterns displayed by the pathogen, newer strategies for combating drug resistance are desperately needed. In the context of TB, such approaches include targeting the efflux capability of the pathogen, modulating the host environment to prevent bacterial drug tolerance, and activating the host anti-mycobacterial pathways. In this review, we discuss the traditional mechanisms of drug resistance in Mtb, newer understandings and the shaping of a set of unconventional approaches to target both the emergence and treatment of drug resistance in TB.

Unlocking the Potential of Trans-Himalayan High-Altitude Seabuckthorn (Hippophae rhamnoides) Plants in the Green Synthesis of Silver Nanoparticles Against Drug-Resistant Foodborne Pathogens: A Step Towards Sustainable Food Safety Goals

Controlling foodborne pathogens is challenging due to the new emergence of antimicrobial resistance to conventional antimicrobials. Therefore, new alternative antimicrobials need to be developed to control foodborne pathogens and avoid microbial resistance. Furthermore, the potential of trans-Himalayan high-altitude seabuckthorn (Hippophae rhamnoides ) plants has not been explored much for the synthesis of silver nanoparticles having antibacterial properties. Hence, this study investigated the development of long-term stable silver nanomaterials using the aqueous extract of seabuckthorn leaves through a green-synthesis approach and evaluated their antibacterial efficacy. These synthesized nanomaterials were characterized along with their stability using UV spectrometry for lambda max ([Formula: see text]) characteristics. Further, the nanoparticles were evaluated for zeta potential (mV), polydispersity index, particle size distribution (nm), electrophoretic mobility ([Formula: see text]mcm/Vs) and conductivity (mS/cm). The seabuckthorn silver nanoparticles are of 260[Formula: see text]nm size and stable (−15[Formula: see text]mV zeta potential) with good antioxidant and antibacterial properties against two typical food pathogens, e.g., Escherichia coli (MTCC 3222) and Salmonella typhimurium (MTCC 3224). Hence, this study developed an eco-friendly, rapid, low-cost green synthesis method for the development of seabuckthorn-coated, stable silver nanoparticles with good antibacterial activity against foodborne pathogens.

Meta-analysis of antimicrobial activity of Allium, Ocimum, and Thymus spp. confirms their promising application for increasing food safety

Biopreservation strategies such as the use of Mediterranean plant extracts to ensure food safety are promising to deal with the emergence of antimicrobial resistances and the overreliance on food chemical additives. In the last few decades, antimicrobial susceptibility testing (AST) for evaluating the in vitro antibacterial potential of plant extracts against the most relevant foodborne pathogens has been widely reported in the literature. The current meta-analysis aimed to summarise and analyse the extensive evidence available in the literature regarding the in vitro antimicrobial capability of Allium, Ocimum and Thymus spp. extracts against foodborne pathogens. A systematic review was carried out to gather data on AST results of these extracts against Listeria monocytogenes, Staphylococcus aureus, Salmonella spp., Escherichia coli and Bacillus cereus, including inhibition diameters (ID) and minimum inhibitory concentrations (MIC). A total of 742 records were gathered from a raw collection of 2,065 articles. Weighted mixed-effect linear models were adjusted to data to obtain pooled ID, pooled MIC and the relationship between both model estimations and observations. The pooled results revealed B. cereus as the most susceptible bacteria to Allium sativum (pooled ID = 20.64 ± 0.61 mm) by diffusion methods and S. aureus (pooled MIC = 0.146 mg/mL) by dilution methods. Diffusion methods did not yield conclusive results for Ocimum spp. extracts; however, the lowest pooled MIC was obtained for S. aureus (0.263 mg/mL). Among the foodborne pathogens evaluated, B. cereus showed the highest sensitivity to Thymus spp. extracts by both diffusion and dilution methods (pooled ID = 28.90 ± 2.34 mm and MIC = 0.075 mg/mL). The methodology used for plant extraction was found to not significantly affect MIC values (p > 0.05). Overall, the antimicrobial effectiveness of the studied extracts against Gram-positive and Gram-negative bacteria was demonstrated. Finally, the robustness of the meta-regression model was confirmed, also revealing an inversely proportional correlation between the ID and MIC measurements (p < 0.0001). These results provide a robust scientific basis on the factors affecting the in vitro antimicrobial efficacy of extracts from Mediterranean plants. They also provide valuable information for stakeholders involved in their industrial application in food, including producers, regulatory agencies and consumers which demand green-labelled foods.

Transmission of antibiotic resistance through organic amendments in arable land: A 3-year field study with pigeonpea–wheat cropping system

The worldwide emergence of antimicrobial resistance (AMR) poses a substantial risk to human health and environmental stability. In agriculture, organic amendments (derived from organic sources such as manure, and plant residues) are beneficial in restoring soil properties and providing essential nutrients to crops but raise concerns about harboring antibiotic resistance, which emphasizes the need for vigilant monitoring and strategic interventions in their application. The current study assessed the impact of farming practices (organic and conventional) in a three-year field experiment with pigeonpea-wheat cropping system, focusing on the transmission of AMR using culture-dependent and -independent approaches, and soil nutrient content. Markers for antibiotic resistance genes (ARGs) (aminoglycoside-aacA, β-lactam-blaTEM, chloramphenicol-cmlA1, macrolide-ermB, sulfonamides-sul1, sul2, and tetracycline-tetO) and integrons (intl1 and intl2) were targeted using qPCR. Manure amendments, particularly FYM1, exhibited a higher abundance of copies of ARGs compared to the rhizospheric soil. Organic farming was associated with higher copies of intl2, sul1, blaTEM, and tetO genes, while conventional farming showed increased copies of sul2 and ermB genes in the rhizosphere. Significant positive correlations were observed among soil nutrient contents, ARGs, and MGEs. The notable prevalence of ARGs linked to manure amendments serves as a cautionary note, demanding responsible management practices.

Mapping the future of antimicrobial use data collection in US animal agriculture: insights from FDA-funded pilot studies.

Antimicrobial use (AMU) contributes to the emergence of antimicrobial resistance, necessitating antimicrobial stewardship actions across all sectors using a One Health approach to preserve antimicrobial effectiveness. This overview delves into 2 FDA-funded projects focused on collecting and analyzing AMU data in major food-producing animal species (cattle, swine, turkeys, and chickens). Initiated in 2016, the projects aimed to establish baseline AMU information and pilot methodologies. This article describes the methodologies used by grantees for data collected from 2016 to 2021, emphasizing the diverse data sources and metrics utilized. Instead of summarizing the trends, it provides a list of publications generated from the grants. Factors contributing to successful data collection included early interaction and trust building between the producers/data holders and researchers. Shared challenges include limitations stemming from convenience sampling, variable industry participation, and lack of data covering all segments of a particular commodity (eg, data on breeding or young animals were lacking). Future collaborative efforts are needed to enhance data standardization, contextualization, representativeness, and reporting of national-scale AMU data going forward. Addressing these challenges and data gaps is essential for effective monitoring of AMU in veterinary settings and animal agriculture, in alignment with national strategies to combat antimicrobial resistance.

Decoding the Structural Diversity: A New Horizon in Antimicrobial Prospecting and Mechanistic Investigation.

The escalating crisis of antimicrobial resistance (AMR) underscores the urgent need for novel antimicrobials. One promising strategy is the exploration of structural diversity, as diverse structures can lead to diverse biological activities and mechanisms of action. This review delves into the role of structural diversity in antimicrobial discovery, highlighting its influence on factors such as target selectivity, binding affinity, pharmacokinetic properties, and the ability to overcome resistance mechanisms. We discuss various approaches for exploring structural diversity, including combinatorial chemistry, diversity-oriented synthesis, and natural product screening, and provide an overview of the common mechanisms of action of antimicrobials. We also describe techniques for investigating these mechanisms, such as genomics, proteomics, and structural biology. Despite significant progress, several challenges remain, including the synthesis of diverse compound libraries, the identification of active compounds, the elucidation of complex mechanisms of action, the emergence of AMR, and the translation of laboratory discoveries to clinical applications. However, emerging trends and technologies, such as artificial intelligence, high-throughput screening, next-generation sequencing, and open-source drug discovery, offer new avenues to overcome these challenges. Looking ahead, we envisage an exciting future for structural diversity-oriented antimicrobial discovery, with opportunities for expanding the chemical space, harnessing the power of nature, deepening our understanding of mechanisms of action, and moving toward personalized medicine and collaborative drug discovery. As we face the continued challenge of AMR, the exploration of structural diversity will be crucial in our search for new and effective antimicrobials.

Methods for screening and evaluation of antimicrobial activity: A review of protocols, advantages, and limitations.

Infectious diseases pose a formidable global challenge, compounded by the emergence of antimicrobial resistance. Consequently, researchers are actively exploring novel antimicrobial compounds as potential solutions. This endeavor underscores the pivotal role of methods employed for screening and evaluating antimicrobial activity-a critical step in discovery and characterization of antimicrobial agents. While traditional techniques such as well-diffusion, disk-diffusion, and broth-dilution are commonly utilized in antimicrobial assays, they may encounter limitations concerning reproducibility and speed. Additionally, a diverse array of antimicrobial assays including cross-streaking, poisoned-food, co-culture, time-kill kinetics, resazurin assay, bioautography, etc., are routinely employed in antimicrobial evaluations. Advanced techniques such as flow-cytometry, impedance analysis, and bioluminescent technique may offer rapid and sensitive results, providing deeper insights into the impact of antimicrobials on cellular integrity. However, their higher cost and limited accessibility in certain laboratory settings may present challenges. This article provides a comprehensive overview of assays designed to characterize antimicrobial activity, elucidating their underlying principles, protocols, advantages, and limitations. The primary objective is to enhance understanding of the methodologies designed for evaluating antimicrobial agents in our relentless battle against infectious diseases. By selecting the appropriate antimicrobial testing method, researchers can discern suitable conditions and streamline the identification of effective antimicrobial agents.