Spread Of Antimicrobial Resistance Research Articles

Changes in incidence and epidemiology of antimicrobial resistant pathogens before and during the COVID-19 pandemic in Germany, 2015–2022

BackgroundCarbapenem-resistant Gram-negative bacteria and methicillin-resistant Staphylococcus aureus (MRSA) are among WHO’s priority pathogens with antimicrobial resistance (AMR). Studies suggest potential impacts of the COVID-19-pandemic on AMR. We described changes in AMR incidence and epidemiology in Germany during the COVID-19-pandemic.MethodsWe used two independent datasets, statutory surveillance and laboratory-based Antibiotic Resistance Surveillance (ARS). We included statutory notifications of infections/colonisations of carbapenem-resistant Acinetobacter spp., Klebsiella pneumoniae, Escherichia coli (CRA/CRKP/CREC) and invasive MRSA. Using Poisson/negative binomial regression and assuming continued pre-pandemic (2015/2017–2020) trends, we projected hypothetical notifications as if the pandemic had not occurred. We quantified annual changes during the pandemic period (2020–2022) by comparing to observed notifications. Additional models considered inpatient reductions, seasonality, infections only, or resistant isolates from ARS.ResultsCRA notified cases were reduced by -30% (95%CI -39%|-20%) in 2020, -23% (-36%|-8%) in 2021, but + 32% (+ 6%|+64%) higher in 2022 relative to hypothetical pre-pandemic projections. Changes were − 35%/-31%/+6% for CRKP, -40%/-61%/-48% for CREC and − 33%/-25%/-20% for MRSA. Statutory-models accounting for fewer inpatients, seasonality and infections only showed similar trends, as did ARS-models for resistant isolates and infections. International mobility for CRA, CRKP and CREC decreased in 2020–2021, then increased in 2022.ConclusionsWe observed significant reductions of AMR notifications and infections during 2020–2021, also when accounting for fewer inpatients. We conclude a genuine reduction of AMR spread occurred during the pandemic. Factors like fewer hospitalisations and reduced international mobility contributed. Rising international mobility may partly explain increases for CRA, CRKP and CREC in 2022. A solid understanding of AMR trends improves infection prevention and control.

Prevalence and dynamics of antimicrobial resistance in pioneer and developing Arctic soils

Antimicrobial resistance (AMR) in soil is an ancient phenomenon with widespread spatial presence in terrestrial ecosystems. However, the natural processes shaping the temporal dissemination of AMR in soils are not well understood. We aimed to determine whether, how, and why AMR varies with soil age in recently deglaciated pioneer and developing Arctic soils using a space-for-time approach. Specifically, we assess how the magnitude and spread of AMR changes with soil development stages, including antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and antibiotic-resistant bacteria (ARB). We showed that ARGs, MGEs, and ARB are present, and exhibit a non-uniform distribution in the developing soils. Their abundance generally increases with soil age but at different rates overall and across different glacier forefields. Our analyses suggest a strong positive relationship between soil age and ARGs and ARB, which we attribute to increased competition between microbes in older soils. We also observed a strong negative relationship between soil age and ARG diversity mediated by soil organic matter – suggesting facilitation due to the alleviation of nutrient limitation. These contrasting results suggest that both competition and facilitation can regulate AMR spread through time in the Arctic, but competition might be the stronger determinant of AMR spread.

The Impact of Wastewater on Antimicrobial Resistance: A Scoping Review of Transmission Pathways and Contributing Factors

Background/Objectives: Antimicrobial resistance (AMR) is a global issue driven by the overuse of antibiotics in healthcare, agriculture, and veterinary settings. Wastewater and treatment plants (WWTPs) act as reservoirs for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs). The One Health approach emphasizes the interconnectedness of human, animal, and environmental health in addressing AMR. This scoping review analyzes wastewater’s role in the AMR spread, identifies influencing factors, and highlights research gaps to guide interventions. Methods: This scoping review followed the PRISMA-ScR guidelines. A comprehensive literature search was conducted across the PubMed and Web of Science databases for articles published up to June 2024, supplemented by manual reference checks. The review focused on wastewater as a source of AMR, including hospital effluents, industrial and urban sewage, and agricultural runoff. Screening and selection were independently performed by two reviewers, with conflicts resolved by a third. Results: Of 3367 studies identified, 70 met the inclusion criteria. The findings indicated that antibiotic residues, heavy metals, and microbial interactions in wastewater are key drivers of AMR development. Although WWTPs aim to reduce contaminants, they often create conditions conducive to horizontal gene transfer, amplifying resistance. Promising interventions, such as advanced treatment methods and regulatory measures, exist but require further research and implementation. Conclusions: Wastewater plays a pivotal role in AMR dissemination. Targeted interventions in wastewater management are essential to mitigate AMR risks. Future studies should prioritize understanding AMR dynamics in wastewater ecosystems and evaluating scalable mitigation strategies to support global health efforts.

Exploring risk factors and antimicrobial susceptibility patterns associated with bacteriuria among Syrian refugees in makeshift camps.

The health and well-being of refugees are critically compromised by harsh living conditions, which foster the emergence of infectious diseases and the misuse of antimicrobial agents. This multicentre cross-sectional community-based study investigated the prevalence of urine carriage of bacteria and the associated antimicrobial resistance patterns among Syrian refugees living in makeshift camps in Lebanon, an East Mediterranean country. We used multivariable logistic regression models to identify the risk factors associated with bacteriuria in this vulnerable population. Mid-stream urine samples were collected aseptically from 79 Syrian refugees; regardless of whether they exhibited symptoms of urinary tract infections. Samples were inoculated onto UriSelect™ 4 chromogenic agar and bacterial isolates were identified using MALDI-TOF-MS. Antibiotic susceptibility testing was assessed using the Kirby-Bauer disk diffusion assay. The prevalence of bacteriuria was 30.8% (95% CI: 21.6-41.7), and the etiologic agents were primarily Escherichia coli (80%), Klebsiella pneumoniae (12%), and Enterobacter cloacae complex (8%). The Enterobacterales isolates exhibited high resistance to penicillins (64%), cephalosporins (20-48%), and quinolones (28%), with 56% showing multidrug resistance. While the female sex and rubbish accumulation were risk factors, tea consumption, reduced chicken intake, and economic support were protective against bacteriuria. This report corroborates prior anecdotal evidence regarding underdiagnosed bacteriuria among Syrian refugees in Lebanon. The data highlight the pressing need for monitoring and awareness programs to curb the spread of infectious diseases and antimicrobial resistance in both refugee and host communities.

Assessing the impact of sewage and wastewater on antimicrobial resistance in nearshore Antarctic biofilms and sediments

BackgroundDespite being recognised as a global problem, our understanding of human-mediated antimicrobial resistance (AMR) spread to remote regions of the world is limited. Antarctica, often referred to as “the last great wilderness”, is experiencing increasing levels of human visitation through tourism and expansion of national scientific operations. Therefore, it is critical to assess the impact that these itinerant visitors have on the natural environment. This includes monitoring human-mediated AMR, particularly around population concentrations such as visitor sites and Antarctic research stations. This study takes a sequencing discovery-led approach to investigate levels and extent of AMR around the Rothera Research Station (operated by the UK) on the Antarctic Peninsula.ResultsAmplicon sequencing of biofilms and sediments from the vicinity of Rothera Research Station revealed highly variable and diverse microbial communities. Analysis of AMR genes generated from long-reads Nanopore MinION sequencing showed similar site variability in both drug class and resistance mechanism. Thus, no site sampled was more or less diverse than the other, either in the biofilm or sediment samples. Levels of enteric bacteria in biofilm and sediment samples were low at all sites, even in biofilm samples taken from the station sewage treatment plant (STP). It would appear that incorporation of released enteric bacteria in wastewater into more established biofilms or associations with sediment was poor. This was likely due to the inactivation and vulnerability of these bacteria to the extreme environmental conditions in Antarctica.ConclusionsOur results suggest minimal effect of a strong feeder source (i.e. sewage effluent) on biofilm and sediment microbial community composition, with each site developing its unique niche community. The factors producing these niche communities need elucidation, alongside studies evaluating Antarctic microbial physiologies. Our data from cultivated bacteria show that they are highly resilient to different environmental conditions and are likely to thrive in a warmer world. Our data show that AMR in the Antarctic marine environment is far more complex than previously thought. Thus, more work is required to understand the true extent of the Antarctic microbiota biodiversity, their associated resistomes and the impact that human activities have on the Antarctic environment.

Antimicrobial Peptides, Their Production, and Potential in the Fight Against Antibiotic-Resistant Pathogens

The article reviews the literature on antimicrobial peptides (AMPs) that exhibit unique antimicrobial mechanisms, such as broad-spectrum activity, low development of antimicrobial resistance, and the ability to modulate the immune response of the host organism. Information is provided on the significant potential of AMPs in the fight against pathogens threatening human health and food safety. Enrichment of the human diet with biologically active peptides obtained using the proteolytic activity of lactic acid bacteria (LAB) is proposed as a simple, accessible, and viable alternative to antibiotics that does not have a harmful side effect. The review briefly covers the methods for obtaining AMPs and features of the LAB proteolytic system responsible for producing bioactive peptides in the environment. It has been shown that using various LAB strains makes it possible to produce high-quality whey-based beverages with different directions of antagonistic activity against opportunistic pathogens and helps optimize the gastrointestinal microbiota. It is assumed that such drinks can reduce the dose of antimicrobials in the combined therapy of various infectious diseases and be a preventive measure against contagion and the spread of antimicrobial resistance.

Oral Antibacterial Drug Prescribing in Primary Care Out-of-Hours Services: A Scoping Review.

The rapid spread of antimicrobial resistance (AMR) presents a critical threat to global health. Primary care plays a significant role in this crisis, with oral antibacterial drugs among the most prescribed medications. Antibacterial prescribing rates are often high and complicated in out-of-hours (OOH) services, including weekdays outside regular hours, weekends, and holidays, potentially exacerbating AMR. This review aims to identify the existing literature on oral antibacterial drug prescribing within primary care OOH services. This review followed established frameworks, adhered to PRISMA-ScR guidelines, and the protocol was registered on Open Science Framework. Seven databases were searched from 2017 to May 2022. Data were summarised, tabulated, and presented narratively to explore themes and patterns that aligned with the review objectives. The search identified 28 studies from nine high-income countries, mainly the UK (n = 6) and Belgium (n = 5). Most were quantitative studies (n = 23). Key areas identified included common oral antibacterial prescriptions, prescribing trends, presentations and conditions managed in OOH services, factors and predictors associated with prescribing, prescribing appropriateness, the impact of interventions on prescribing, prescribing in the context of COVID-19, patient satisfaction and expectations, and the challenges encountered, such as factors influencing prescribing behaviour and decision making, safety netting, and communication. This review highlights key areas around oral antibacterial prescribing in primary care OOH services. Despite the numerous articles identified covering various areas within OOH services, the variability in OOH services approaches across countries and studies complicates the comparison of practice. Further research is needed to better understand practices in these settings.

Educate, Advocate, Act Now: a sustainable approach to combating antimicrobial resistance TODAY.

Antimicrobial resistance (AMR) poses a great challenge to health systems all over the world. It is exacerbated by the abuse, misuse and overuse of antimicrobials in humans, animals, plants and the environment. This viewpoint emphasizes the critical need to address the challenges of AMR through an integrated, long-term approach that focuses on education, advocacy and collective action. This article stresses that the fight against AMR is not a battle for governments and scientists alone but requires engagement at every level. The article concludes that we can reduce the spread of AMR by exploring the potential of education, advocacy and collective action.

N-Acetyl cysteine exhibits antimicrobial and anti-virulence activity against Salmonella enterica.

Salmonella enterica is a common foodborne pathogen that causes intestinal illness varying from mild gastroenteritis to life-threatening systemic infections. The frequency of outbreaks due to multidrug-resistant Salmonella has been increased in the past few years with increasing numbers of annual deaths. Therefore, new strategies to control the spread of antimicrobial resistance are required. In this work, we found that N-acetyl cysteine (NAC) inhibits S. enterica at MIC of 3 mg ml-1 and synergistically activates the bactericidal activities of common antibiotics from three-fold for ampicillin and apramycin up to1000-fold for gentamycin. In addition, NAC inhibits the expression of virulence genes at sub-inhibitory concentrations in a dose-dependent manner. The whole-genome sequencing revealed that continuous exposure of S. enterica to NAC leads to the development of resistance; these resistant strains are attenuated for virulence. These results suggest that NAC may be a promising adjuvant to antibiotics for treating S. enterica in combination with other antibiotics.

An eco-evolutionary perspective on antimicrobial resistance in the context of One Health.

The One Health approach musters growing concerns about antimicrobial resistance due to the increased use of antibiotics in healthcare and agriculture, with all of its consequences for human, livestock, and environmental health. In this perspective, we explore the current knowledge on how interactions at different levels of biological organization, from genetic to ecological interactions, affect the evolution of antimicrobial resistance. We discuss their role in different contexts, from natural systems with weak selection, to human-influenced environments that impose a strong pressure toward antimicrobial resistance evolution. We emphasize the need for an eco-evolutionary approach within the One Health framework and highlight the importance of horizontal gene transfer and microbiome interactions for increased understanding of the emergence and spread of antimicrobial resistance.

Shallow Shotgun Sequencing of Healthcare Waste Reveals Plastic-Eating Bacteria with Broad-Spectrum Antibiotic Resistance Genes

The burgeoning crises of antimicrobial resistance and plastic pollution are converging in healthcare settings, presenting a complex challenge to global health. This study investigates the microbial populations in healthcare waste to understand the extent of antimicrobial resistance and the potential for plastic degradation by bacteria. Our metagenomic analysis, using both amplicon and shallow shotgun sequencing, provided a comprehensive view of the taxonomic diversity and functional capacity of the microbial consortia. The viable bacteria in healthcare waste samples were analyzed employing full-length 16S rRNA sequencing, revealing a diverse bacterial community dominated by Firmicutes and Proteobacteria phyla. Notably, Proteus mirabilis VFC3/3 and Pseudomonas sp. VFA2/3 were detected, while Stenotrophomonas maltophilia VFV3/2 surfaced as the predominant species, holding implications for the spread of hospital-acquired infections and antimicrobial resistance. Antibiotic susceptibility testing identified multidrug-resistant strains conferring antimicrobial genes, including the broad-spectrum antibiotic carbapenem, underscoring the critical need for improved waste management and infection control measures. Remarkably, we found genes linked to the breakdown of plastic that encoded for enzymes of the esterase, depolymerase, and oxidoreductase classes. This suggests that specific bacteria found in medical waste may be able to reduce the amount of plastic pollution that comes from biological and medical waste. The information is helpful in formulating strategies to counter the combined problems of environmental pollution and antibiotic resistance. This study emphasises the importance of monitoring microbial communities in hospital waste in order to influence waste management procedures and public health policy. The findings highlight the need for a multidisciplinary approach to mitigate the risks associated with antimicrobial resistance and plastic waste, especially in hospital settings where they intersect most acutely.

Wastewater monitoring - passive sampling for the detection of SARS-CoV-2 and antibiotic resistance genes in wastewater.

As a lesson learned from the COVID-19 pandemic, wastewater-based epidemiology was recognised and used as an important method for surveillance and early detection of SARS-CoV-2. As a result, consideration of wastewater as a source of public health information has gained new prominence, and there is consensus that similar approaches can be used to detect the spread of other viral pathogens or antimicrobial resistance (AMR) in populations. However, the implementation of wastewater monitoring poses challenges in terms of obtaining representative and meaningful samples. In particular, it is difficult to sample small catchments, critical facilities (e.g. hospitals) or low-income countries where the use of automatic water samplers is not possible or the samplers are not available. To overcome these problems, this study developed a low-cost and easy-to-use passive sampler based on activated carbon as an adsorbent with a corresponding elution/extraction protocol that allows the detection of viruses and antibiotic resistance genes in wastewater. Monitoring of SARS-CoV-2 with these passive samplers at the influent of a wastewater treatment plant over a period of 1.5months showed a positive correlation with monitoring with 24-h composite samples in the catchment area. Analysis of the nucleic acid extracts for antibiotic resistance genes showed the presence of clinically relevant carbapenemase genes such as blaKPC-3 and blaNDM-1 in the wastewater samples, with these genes being detected more reliably by the passive samplers than in the 24-h composite samples. This study therefore demonstrated that passive samplers provide reproducible SARS-CoV-2 RNA and antibiotic resistance gene signals from wastewater and a time-integrated measurement of the sampled matrix with high sensitivity.

Wastewater-based analysis of antimicrobial resistance at UK airports: Evaluating the potential opportunities and challenges.

With 40 million annual passenger flights, airports are key hubs for microbial communities from diverse geographic origins to converge, mix, and distribute. Wastewater derived from airports and aircraft represent both a potential route for the global dispersion of antimicrobial resistant (AMR) organisms and an under-utilised resource for strengthening global AMR surveillance. This study investigates the abundance and diversity of antimicrobial resistance genes (ARGs) in wastewater samples collected from airport terminals (n=132), aircraft (n=25), and a connected wastewater treatment plant (n=11) at three international airports in the UK (London Heathrow, Edinburgh and Bristol). A total of 76 ARGs were quantified using high throughput qPCR (HT-qPCR) while a subset of samples (n=30) was further analysed by metagenomic sequencing. Our findings reveal that aircraft wastewater resistomes were compositionally distinct from those observed at airport terminals, despite their similar diversity. Notably, flights originating from Asia and Africa carried a higher number of unique ARGs compared to those from Europe and North America. However, clustering of the ARG profile displayed no overall association with geography. Edinburgh terminal and pumping station wastewater had compositionally comparable resistomes to that of the connected urban wastewater treatment plant, though further research is needed to determine the relative contributions of the local population and international travellers. This study provides the first comprehensive investigation of AMR in wastewater from both aircraft and terminals across multiple international airports. Our results highlight aircraft wastewater as a potential route for cross-border AMR transmission and a valuable tool for global AMR surveillance. However, the findings also underscore the limitations and need for standardised approaches for AMR monitoring in airport environments, to effectively mitigate the global spread of AMR and enhance public health surveillance strategies.

Recent Advances in Antimicrobial Resistance: Insights from Escherichia coli as a Model Organism.

Antimicrobial resistance (AMR) represents a critical global health threat, and a thorough understanding of resistance mechanisms in Escherichia coli is needed to guide effective treatment interventions. This review explores recent advances for investigating AMR in E. coli, including machine learning for resistance pattern analysis, laboratory evolution to generate resistant mutants, mutant library construction, and genome sequencing for in-depth characterization. Key resistance mechanisms are discussed, including drug inactivation, target modification, altered transport, and metabolic adaptation. Additionally, we highlight strategies to mitigate the spread of AMR, such as dynamic resistance monitoring, innovative therapies like phage therapy and CRISPR-Cas technology, and tighter regulation of antibiotic use in animal production systems. This review provides actionable insights into E. coli resistance mechanisms and identifies promising directions for future antibiotic development and AMR management.

Antibiotic use at the Centre Hospitalier Universitaire de Zone d'Abomey Calavi/Sô-Ava (CHUZ/AS) in Benin: a point prevalence survey.

Antimicrobial stewardship promotes the appropriate use of antibiotics to prevent the emergence and spread of antimicrobial resistance. This study evaluated the use of antibiotics using a point prevalence survey at the Centre Hospitalier Universitaire de Zone d'Abomey Calavi/Sô-Ava (CHUZ/AS) in Benin. This cross-sectional study utilized the WHO point prevalence survey methodology for monitoring antibiotic use among inpatients in hospitals. The survey was conducted from 11 January 2022 to 19 January 2022 among hospitalized patients before 8:00 a.m. on the day of the survey. Of the 111 inpatient medical files reviewed, the prevalence of antibiotic use was 82.9%. The number of antibiotics received per patient ranged from 1 to 5, with a mean of 2.45 ± 1.11 and a median of 2. The most commonly prescribed class of antibiotics was beta-lactams (46.7%), aminoglycosides (20.6%) and nitroimidazoles (19.7%). According to the WHO AWaRe classification, 30.4% of inpatients received the Access group of antibiotics and 44% received a combination of Access and Watch group antibiotics; treatment was empiric in 94.5% of encounters. Only 22.7% of patients were treated based on microbiological examination/culture and sensitivity testing. This study found a high prevalence of antibiotic use among inpatients at the CHUZ/AS Tertiary Care Hospital in Benin. The most prescribed antibiotics were ampicillin, metronidazole and ceftriaxone. Consequently, the study found a low use of culture and sensitivity testing to guide treatment, particularly in the paediatric and surgical population, and the preference for broad-spectrum antibiotics suggests that antibiotic use at the CHUZ/AS Tertiary Care is not optimal. Therefore, antimicrobial stewardship programmes, policies and guidelines must be instigated and strengthened to address these gaps and promote rational use of antibiotics.

Epidemiology of Antimicrobial-Resistant Diarrheagenic Escherichia coli Pathotypes From Children, Livestock and Food in Dagoretti South, Nairobi Kenya.

Peri-urban environments, characterized by dense human populations, cohabiting livestock, and complex food systems, serve as hotspots for food contamination and infectious diseases. Children aged 6-24 months are particularly vulnerable, as they often encounter contaminated food and water, increasing their risk of food-borne disease, with diarrhea being a common symptom. We investigated the prevalence of antimicrobial resistance (AMR) in pathogenic Escherichia coli from children 6-24 months of age, their food, and cohabiting livestock, in Dagoretti South subcounty in Nairobi, Kenya. Of 540 stools, 296 livestock feces, and 859 food samples collected from 585 randomly enrolled households, 16% harbored diarrheagenic E. coli (DEC) pathotypes. The predominant AMR phenotypes observed were trimethoprim-sulfamethoxazole, ampicillin, and tetracycline at 53%, 48% and 41%, respectively. Diarrheagenic E. coli from children showed significantly higher resistance to all antibiotics compared to those from livestock and food. Overall, 30% of the 274 DEC isolates from all three sources exhibited multidrug resistance. Network analysis of AMR co-occurrence revealed two clusters: (1) ampicillin, trimethoprim-sulfamethoxazole, tetracycline, amoxicillin/clavulanic acid, and chloramphenicol; and (2) nalidixic acid, ciprofloxacin, gentamicin, and ceftriaxone. The co-resistance backbone of ampicillin-trimethoprim/sulfamethoxazole-tetracycline was significantly higher among isolates from children than from other hosts (χ² = 29.858, df = 2, adjusted P < 0.05). Logistic regression analysis revealed that on-site disposal of animal manure and garbage, along with a recent history of diarrhea, were significantly associated with AMR carriage in children (P < 0.05). These findings emphasize the need for One Health interventions to curb emergence and spread of AMR in these close-contact populations.

Evolutionary and functional divergence of Sfx, a plasmid-encoded H-NS homolog, underlies the regulation of IncX plasmid conjugation.

Conjugative plasmids are widespread among prokaryotes, highlighting their evolutionary success. Conjugation systems on most natural plasmids are repressed by default. The negative regulation of F-plasmid conjugation is partially mediated by the chromosomal nucleoid-structuring protein (H-NS). Recent bioinformatic analyses have revealed that plasmid-encoded H-NS homologs are widespread and exhibit high sequence diversity. However, the functional roles of most of these homologs and the selective forces driving their phylogenetic diversification remain unclear. In this study, we characterized the functionality and evolution of Sfx, a H-NS homolog encoded by the model IncX2 plasmid R6K. We demonstrate that Sfx, but not chromosomal H-NS, can repress R6K conjugation. Notably, we find evidence of positive selection acting on the ancestral Sfx lineage. Positively selected sites are located in the dimerization, oligomerization, and DNA-binding interfaces, many of which contribute to R6K repression activity-indicating that adaptive evolution drove the functional divergence of Sfx. We additionally show that Sfx can physically interact with various chromosomally encoded proteins, including H-NS, StpA, and Hha. Hha enhances the ability of Sfx to regulate R6K conjugation, suggesting that Sfx retained functionally important interactions with chromosomal silencing proteins. Surprisingly, the loss of Sfx does not negatively affect the stability or dissemination of R6K in laboratory conditions, reflecting the complexity of selective pressures favoring conjugation repression. Overall, our study sheds light on the functional and evolutionary divergence of a plasmid-borne H-NS-like protein, highlighting how these loosely specific DNA-binding proteins evolved to specifically regulate different plasmid functions.IMPORTANCEConjugative plasmids play a crucial role in spreading antimicrobial resistance and virulence genes. Most natural conjugative plasmids conjugate only under specific conditions. Therefore, studying the molecular mechanisms underlying conjugation regulation is essential for understanding antimicrobial resistance and pathogen evolution. In this study, we characterized the conjugation regulation of the model IncX plasmid R6K. We discovered that Sfx, a H-NS homolog carried by the plasmid, represses conjugation. Molecular evolutionary analyses combined with gain-of-function experiments indicate that positive selection underlies the conjugation repression activity of Sfx. Additionally, we demonstrate that the loss of Sfx does not adversely affect R6K maintenance under laboratory conditions, suggesting additional selective forces favoring Sfx carriage. Overall, this work underscores the impact of protein diversification on plasmid biology, enhancing our understanding of how molecular evolution affects broader plasmid ecology.

Comparative Genome Analysis of Canine Frederiksenia canicola Isolates.

Background/Objectives: The One Health approach is crucial for managing and controlling the spread of antimicrobial resistance. Frederiksenia canicola is a recently identified bacterial species that seems to be a component of the oral microbiota of dogs; however, its pathogenic nature is questionable. Methods: In this study, the antibacterial susceptibility of F. canicola isolates was determined using the disk diffusion and broth microdilution methods. Genome-wide comparative analyses were performed to identify the genetic factors driving virulence and antimicrobial drug resistance (e.g., virulence factors, antimicrobial resistance genes (ARGs) and prophage-related sequences). Results: Most of the F. canicola isolates lacked virulence-associated genes. F. canicola is likely resistant to clindamycin, lincomycin and neomycin, but susceptible to penicillin, erythromycin and enrofloxacin. Antimicrobial resistance genes were not found in the F. canicola genomes, but prophage-related sequences were identified, suggesting its potential in the transfer of genes associated with drug resistance between bacteria in the oral microbiome. Conclusions: F. canicola is presumably a commensal organism with low virulence potential, as evidenced by the absence of virulence-associated genes. As F. canicola can colonize a wide range of hosts, including humans, further investigation with a greater number of isolates is needed to better understand the role of F. canicola in disease development and the spread of drug resistance.

Nanocarrier Mediated Molecular Taregting Strategies For iCD4 Receptors to Combat Anti-microbial Resistance

The emergence and spread of Antimicrobial Resistance (AMR) pose a grave threat to global public health. In the pursuit of innovative solutions, targeting the immune cell CD4 receptors (iCD4) has gained momentum as a potential strategy for combating AMR. This abstract explores drug delivery strategies aimed at harnessing iCD4 receptors to enhance the efficacy of antimicrobial therapies. The CD4 receptor, primarily found on the surface of T-helper lymphocytes, plays a pivotal role in immune responses. Recent research has revealed that iCD4 receptors are also expressed on other immune cells, such as macrophages and dendritic cells, which are integral in the host's defense against pathogens. Leveraging these receptors as drug targets opens new avenues for the precise delivery of antimicrobial agents. Various drug delivery systems, including nanoparticles, liposomes, and antibody- drug conjugates, can be engineered to specifically target iCD4 receptors. These carriers offer improved drug stability, controlled release, and reduced side effects. Furthermore, the functionalization of these carriers with ligands that bind selectively to iCD4 receptors ensures targeted drug delivery to infected tissues. In summary, drug delivery strategies that target iCD4 receptors hold immense promise for combatting AMR. By delivering antimicrobial agents directly to immune cells involved in the host defense, we can potentially enhance therapeutic efficacy, reduce side effects, and mitigate the emergence of resistance. This approach represents a promising avenue for the development of innovative treatments to address the urgent global challenge of antimicrobial resistance.

Minimum inhibitory concentrations of extended spectrum cephalosporins: A systematic review and meta-analysis of Neisseria gonorrhoeae treatment failures.

Neisseria gonorrhoeae is one of the recognised global antimicrobial resistance priorities. Extended spectrum cephalosporins, the last remaining reliable antimicrobial, increasingly fail to clear N. gonorrhoeae infections, especially pharyngeal gonorrhoea, leading to limited future treatment options. We conducted a systematic review and meta-analysis of gonococcal treatment failures and compared the minimum inhibitory concentrations (MIC) of isolates from pharyngeal and extra-pharyngeal anatomical sites (PROSPERO registration: CRD42020189101). The overall pooled mean MIC for cefixime was 0.17 mg/L (95% [CI]: 0.07, 0.41) and ceftriaxone was 0.10 mg/L (95% [CI]: 0.05, 0.22). For cefixime, the mean MIC estimates for pharyngeal and extra-pharyngeal treatment failures were 0.05 mg/L (95% [CI]: 0.02, 0.14) and 0.29 mg/L (95% [CI]: 0.11, 0.81), and for ceftriaxone 0.09 mg/L (95% [CI]: 0.03, 0.22) and 0.14 mg/L (95% [CI]: 0.03, 0.73), respectively. The pooled mean MICs for pharyngeal isolates are below the phenotypic European Committee on Antimicrobial Susceptibility Testing (EUCAST) resistance breakpoint for both antimicrobials (>0.125 mg/L). Our findings underscore the need to review the current resistance breakpoints used for pharyngeal infection and the urgency to establish international standards for MIC testing, and advance efforts of the World Health Organization's global action plan to control the spread and impact of antimicrobial resistance in N. gonorrhoeae. Ongoing susceptibility testing of gonococcal isolates and surveillance of treatment failures are central to informing appropriate public health responses.