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Antimicrobial resistance (AMR) is a major global health concern, involving complex transmission pathways linking humans, domestic animals, wildlife, and the environment. Wild animals and plants can harbour and transmit AMR, while also serving as sentinels. Here, we aimed to evaluate current knowledge and research gaps on AMR in wild animals and plants to inform One Health research and policy. We conducted a semi‑systematic review of AMR in wild animals and plants, generating a dataset of 866 publications and analysing metadata on host taxa, microbial and genetic targets, and analytical approaches. The literature shows strong taxonomic, geographic, and methodological biases, with mammals and birds dominating, whereas plants (n = 14) and amphibians (n = 10) were rarely studied. Resistant fungi were also under‑represented (2% of studies), while Escherichia spp. accounted for 33% of microbial targets. Employing wildlife‑based surveillance offers a useful policy tool to address key AMR gaps at human-animal-environment interfaces.

Antimicrobial resistance (AMR) is a major public health threat, especially in low- and middle-income countries (LMICs), where large datasets linking antimicrobial susceptibility testing (AST) with genomic data remain limited. We analyzed AST results and whole genomes from 266 resistant bacterial isolates representing diverse species and specimen sources, collected from Northern and Western India between 2022 and 2024. Correlation of genomic resistance predictions with AST data revealed an overprediction of resistance by genomic methods. To our knowledge, this is the first study to systematically examine these discrepancies across multiple antibiotic-pathogen combinations in India and to identify promising targets for genomic resistance prediction. We also investigated the predominant antibiotic resistance genes (ARGs), plasmids, and other mobile genetic elements associated with them. Overall, our findings contribute meaningfully to the genomic epidemiology of AMR in India and support the development of molecular diagnostics for antimicrobial resistance.

Understanding all sources of selective pressure that contribute to the emergence of antibiotic resistance is essential for developing sustainable antimicrobial strategies. Here, we investigated the interaction between phage T4 and Escherichia coli MG1655 to determine whether mutations conferring phage resistance also shape the genetic background for β-lactam resistance. Using experimental evolution, whole-genome sequencing, and targeted genetic reconstructions, we identified mutations in porins and lipopolysaccharide (LPS) biosynthesis as the predominant routes to phage T4 resistance. Precise allelic replacements and isogenic strain comparisons demonstrated that these mutations not only protect against phage predation but also create a genetic context that facilitates the emergence of β-lactam resistance, including resistance to carbapenems. Together, these findings provide compelling evidence that phage-driven selection can establish bacterial genetic backgrounds predisposed to antibiotic resistance. This work highlights the evolutionary risks associated with phage therapy and underscores the need to account for genetic trade-offs when developing alternative antimicrobial strategies.

Patients with advanced chronic liver disease who have underlying cirrhosis are highly susceptible to bacterial infections, which significantly increase the risk of complications and mortality, compounded by escalating antimicrobial resistance. The current gold standard for infection detection and antimicrobial resistance (AMR) profiling remains dependant on traditional microbiological methods. These conventional approaches are slow, labour-intensive, and often fail to deliver timely and accurate results, delaying critical antimicrobial treatment decisions. Clinical metagenomics (CMg) is emerging as a transformative molecular-based tool in infection diagnostics. By enabling the direct sequencing of pathogens from patient-derived samples, CMg offers rapid and comprehensive identification of pathogens and their resistance profiles. Incorporating this technology into the clinical management of patients with cirrhosis has potential to address diagnostic challenges, reduce reliance on broad-spectrum antibiotics and improve outcomes. To effectively incorporate CMg into infection diagnostics, it will be essential to embed of point-of-care sequencing, standardisation of AMR databases, and accessibility to bioinformatics workflows.

Antimicrobial resistance poses a significant global health threat. Experimental evolution studies are crucial in understanding resistance mechanisms and thereby informing strategies to preserve antibiotic efficacy. We developed a novel continuous experimental evolution system enabling uninterrupted medium exchange with a rising antibiotic gradient, using standard laboratory equipment. We applied this system to three Enterobacter cloacae complex strains isolated from urinary tract infections in Germany between 1990 and 1992, which therefore had no prior exposure to cefepime, a fourth-generation cephalosporin approved in Germany in 2004. After four days of exposure to a cefepime gradient, resistant mutants emerged in all three strains. Notably, one mutant exhibited cross-resistance to the novel antibiotics cefiderocol and ceftazidime-avibactam, due to a single missense mutation in the β-lactamase gene blaMIR-11. Our study demonstrates the effectiveness of this novel approach for investigating antimicrobial resistance development and cross-resistance mechanisms, as well as identifying and characterizing a mutation attributed to major cross-resistance.

Fungal antimicrobial resistance (fAMR) is accelerating, driven in part by the dual-use of antifungal modes of action in agriculture and medicine, threatening therapy. Addressing this challenge requires a unified One Health response that balances agricultural productivity, economic stability, and human and animal health. By focusing on the United Kingdom's policy approach, we argue that current efforts are constrained by fragmented governance, surveillance and regulation. To resolve this, we propose three policy recommendations: 1. a cross-government fAMR body, 2. mandatory environmental and clinical surveillance, and 3. for fungicide approvals to look beyond crop pathogens and integrate risk assessments for potential hotspots of resistance selection in human fungal pathogens. These measures will safeguard current and future antifungals while providing much-needed regulatory clarity and will be translatable to other national and regional contexts.

The identification of the determinants driving antimicrobial resistance is a prerequisite for improving the control of resistance emergence and dissemination. Disinfectant biocides, daily used in food-processing industries, have already been associated with the cross-selection of antibiotic-resistant bacterial populations. However, very few studies have addressed this issue using a biofilm model, the predominant bacterial lifestyle in food-processing environments. In this work, we examined the adaptation of Escherichia coli biofilms to four biocidal active substances over one month, and assessed their subsequent effects on antibiotic resistance. Exposure to N-(3-aminopropyl)-N-dodecylpropane-1,3-diamine (TMN) and benzalkonium chloride significantly increased the emergence of rifampicin-resistant (RifR) variants in biofilms. Genomic analyses revealed that the RifR variants selected upon TMN exposure recurrently harboured mutations in genes related to lipopolysaccharide (LPS) biosynthesis that conferred low-level rifampicin resistance in biofilm. These variants displayed altered LPS profiles, a more negative surface charge, and reduced membrane permeability. Proteomic and phenotypic analyses supported a metabolic reorientation of envelope sugar precursors, with decreased modulation of LPS synthesis and a marked induction of the colanic acid biosynthetic pathway in TMN-selected variants. This shift resulted in increased matrix production and reinforced biofilm-associated tolerance. Together, these data identify outer membrane reprogramming, linking LPS modulation with colanic acid overproduction, as a previously unknown mechanism of TMN adaptation that simultaneously promotes antibiotic cross-resistance in E. coli biofilms.

The global spread of New Delhi metallo-β-lactamase (NDM)-producing Gram-negative bacteria poses a major threat to healthcare systems worldwide, yet the processes driving their long-term establishment at national scales remain poorly understood. Here, we integrate a decade of nationwide surveillance with high-resolution genomics to reconstruct the emergence, dissemination, and evolution of blaNDM in Costa Rica, from its first detection in 2014 to a major hospital outbreak during the COVID-19 pandemic. National surveillance confirmed hundreds of blaNDM-positive isolates, revealed widespread dissemination across hospitals, and identified a temporal shift in dominant blaNDM hosts from 2020 onwards. During the pandemic, increased NDM detection coincided with a large intrahospital outbreak involving 247 patients with a 51% case-fatality rate. Genomic analysis of 40 representative isolates revealed both plasmid- and chromosome-associated blaNDM-1-carriage and heterogeneous dissemination through globally disseminated high-risk and locally emerging clones. Plasmid-resolved analyses showed that the dominant IncA/C2 blaNDM-1-carrying plasmid derived from a globally conserved backbone and diversified into multiple circulating variants and fusion events with IncF elements, generating multidrug-resistant megaplasmids. Together, these findings highlight how global connectivity, local population dynamics, and plasmid plasticity interact to drive the national persistence of blaNDM and underscore the importance of sustained genomic surveillance.

Antimicrobial resistance (AMR) is increasingly reported in wildlife, yet evidence from Africa remains fragmented. We conducted a systematic review of AMR in African wildlife, screening 4,802 records and including 61 studies from 21 countries. Phenotypic testing was performed in all studies, primarily using disk diffusion (82%), with genotypic assays in 86.8%. Across 4,669 bacterial isolates from 27 eligible studies, the pooled prevalence of phenotypic resistance was 59% (95% CI: 34-80%), with substantial heterogeneity (I² = 97.4%). Wild birds exhibited the highest pooled prevalence (93%), followed by non-human primates (35%) and herbivores (25%). Escherichia coli (20 studies and 3414 isolates) showed a pooled resistance prevalence of 62%. Pooled multidrug resistance was 23.1% (9 studies and 1128 isolates). Sampling was predominantly opportunistic and concentrated in human-impacted environments, limiting ecological inference. These findings highlight significant AMR occurrence across diverse wildlife taxa and substantial gaps in surveillance, coverage, and methodological consistency.

Black soldier fly larvae (BSFL) are promising for converting animal manure into protein; however, the risk of antibiotic resistance gene (ARG) enrichment in the larval gut during this process remains unclear. Here, we employed metagenomic and metatranscriptomic analyses to investigate this risk during BSFL conversion of duck manure. Our results demonstrated that within the BSFL treatment system, ARG abundance and diversity in manure decreased significantly over time. Concurrently, total abundance and transcriptional activity of ARGs in the larval gut were significantly lower than those in manure. However, comparative sequence analysis suggested the potential for ARG exchange between bacterial communities in manure and larval gut. Klebsiella, Escherichia, Citrobacter, and Pseudomonas were identified as the primary hosts in the gut. The enrichment and dynamics of these manure-derived ARGs were jointly driven by shifts in physicochemical properties (notably organic matter and total nitrogen), mobile genetic elements, and the bacterial community. Validation experiments demonstrated that modulating these key physicochemical drivers can mitigate ARG abundance in the larval gut. Overall, this study highlights the potential enrichment risk of manure-derived ARGs in the BSFL gut, identifies key hosts and drivers, and provides actionable mitigation strategies for safer BSFL application.

The use of antimicrobials in livestock farming drives selection and dissemination of antimicrobial resistance (AMR), prompting implementation of veterinary stewardship programs to reduce antimicrobial usage (AMU). We evaluated changes in AMR on 45 Dutch pig farms before and after tailored, coaching-based interventions using phenotypic testing of Escherichia coli and metagenomic profiling of pooled faeces. Post-weaning pig farms, including nursery and fattening units, entered the intervention in a stepped-wedge design, with intervention periods ranging from 10 to 27 months. Across farms, AMU and abundances of several antimicrobial resistance gene classes declined over time, alongside reductions in overall resistome levels. Proportions of phenotypic AMR in E. coli were more variable, although decreased AMU was associated with lower resistance for specific antimicrobial classes, such as tetracyclines and beta-lactams. While longer follow-up is required to fully assess long-term impacts, these findings indicate that veterinary antimicrobial stewardship programs can yield measurable short-term reductions in AMR at farm level.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant public health threat due to both extensive antimicrobial resistance and immune evasion capabilities, necessitating alternative therapeutic strategies. Disruption of bacterial metal ion homeostasis, a process already leveraged by host nutritional immunity, represents a promising therapeutic approach. The synthetic ionophore PBT2 delivers zinc (Zn) directly into the bacterial cytosol, where it can dysregulate cellular processes and restore the efficacy of conventional antibiotics. Here, we use PBT2 and Zn (PZ) to study the cellular response to metal dysbiosis in MRSA, identifying new metal-dependent molecular vulnerabilities. Integrated transcriptomics, metabolomics and molecular analyses revealed that the antibacterial and oxacillin-resensitisation action of PZ is driven by dual metal stress: intracellular Zn accumulation and manganese (Mn) depletion. PZ disrupted central carbon metabolism at multiple key nodes, impairing glycolysis, the TCA cycle and respiration, leading to NADH and ATP depletion and compromised peptidoglycan biosynthesis. PZ also altered the metal-dependent oxidative stress response, resulting in superoxide accumulation. Collectively, this work presents the dynamic interplay between bacterial metal ion homeostasis, central metabolism, and β-lactam resistance. Uncovering how PBT2 subverts the adaptive responses of MRSA to host-imposed stresses contributes to our understanding of host-pathogen interactions and offers a foundation for developing novel antimicrobials based on metal homeostasis disruption.

River biofilms are frequently exposed to invasion by antibiotic-resistant bacteria (ARB) due to episodic or chronic wastewater inputs, yet the ecological processes governing the fate of invaders and their resistance plasmids remain poorly understood. We experimentally exposed river-grown biofilms from sites differing in microbial diversity and wastewater impact to a genetically tagged ARB Escherichia coli carrying a transferable IncPα plasmid with the nptII resistance gene. Over two weeks, we tracked invader and plasmid dynamics using qPCR and plasmid-to-genome ratios as a proxy for horizontal gene transfer (HGT), complemented by 16S rRNA gene sequencing and metagenomics. Both quantification approaches yielded consistent results: the invader transiently established in all biofilms, peaking within 48 h and declining to near-background levels after 14 days. Decreasing plasmid-to-genome ratios indicated limited HGT and progressive plasmid loss. Biofilms impacted by wastewater showed slower declines, suggesting greater plasmid persistence in disturbed environments and increased abundance of specific indigenous antimicrobial resistance genes of public health concern. While the overall resistome exhibited short-lived shifts, and indigenous resistomes remained largely stable. These findings demonstrate that invader-biofilm interactions are dynamic and shaped by community context, supporting the One Health framework and highlighting how environmental conditions modulate antimicrobial resistance risks in freshwater ecosystems.

Antifungal tolerance, unlike resistance, allows cells to grow slowly at concentrations above the minimum inhibitory concentration. While resistance mechanisms are well characterized, the pathways underlying tolerance remain elusive. Here, we performed a genetic screen of a transcriptional factor mutant library to identify regulators of azole tolerance in Candida albicans. This screen uncovered Isw2, the catalytic subunit of the ISW2 ATP-dependent chromatin remodeling complex, as a negative regulator of azole tolerance. Integrating transcriptomics, Isw2 DNA-binding profiles, and nucleosome-occupancy analyses revealed that Isw2 maintains a repressive chromatin architecture at the CRZ1 promoter, limiting the nucleosome-depleted region and suppressing CRZ1 transcription. Isw2 also modulates fluconazole heteroresistance and amphotericin B sensitivity through Crz1. In addition, we identified the copper-responsive transcription factor Mac1 as a context-dependent regulator of azole tolerance, acting negatively under copper limitation but positively under copper-replete conditions. Together, these findings reveal unexpected roles for chromatin remodeling and copper homeostasis in antifungal tolerance.

Tuberculosis (TB), the deadliest infectious disease globally, still poses an enormous public health challenge exacerbated by the rise of multi-drug resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains. The bicyclic nitroimidazoles pretomanid (PTM) and delamanid (DLM) represent the most recent class of anti-tubercular compounds to achieve regulatory approval and clinical implementation in TB chemotherapy regimens. Both are prodrugs whose activity relies on the deazaflavin-dependent nitroreductase Ddn. High-throughput screening on a clinically relevant DdnL49P mutant reveals molecules capable of restoring PTM activity. Optimisation through rational medicinal chemistry leads to highly potent compounds capable of drastically reducing the MIC of PTM while improving its bactericidal activity. Mechanistic studies using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), transposon sequencing and thin-layer chromatography of radiolabeled extracted lipids show that these molecules do not trigger bioactivation pathways, but instead target a compensatory pathway involving Rv2073c, an enzyme that is redundant with DprE2 for bacterial cell wall biosynthesis. The concomitant perturbation of both the DprE2- and Rv2073c-dependent steps by the PTM-NAD adduct and optimised norbornene derivatives leads to a collapse in arabinan synthesis correlating with bacterial death. This study thus highlights Rv2073c as a promising vulnerability that can be exploited to potentiate the efficacy of nitroimidazole anti-tuberculosis drugs.

The prevalence and proliferation of antimicrobial-resistant bacteria is considered one of the critical issues of our time. Wastewater is a habitat for complex microbial communities where bacteria share antimicrobial-resistance genes through horizontal gene transfer. Hospital wastewater plumbing systems are an ideal reservoir for environmental and pathogenic bacteria to interface and exchange antimicrobial-resistance genes. Replacement of contaminated plumbing may be the most intuitive and widely deployed response to the detection and colonization of highly-resistant potentially pathogenic bacteria in hospital sink drains. In this study, we analyzed sink-drain biofilms from six intensive-care patient rooms using shotgun metagenomic sequencing and microbial culture. We show an evident shift in biofilm community structure toward increased abundance of Enterobacteriaceae following plumbing replacement. Higher resistome load and abundance of clinically relevant resistance and typically encountered mobile genes in the newly replaced plumbing was also observed. Taken together, these finding suggest that exchanging contaminated plumbing for new plumbing may actually have the unexpected consequence of increased abundance of Enterobacterales and antimicrobial-resistance genes in the sink drains. Disruption of preexisting complex environmental biofilms may result in an unintended microbial population shifts and a potential subsequent increase in the amount of antimicrobial-resistant Enterobacterales which are targeted for elimination.

Aquatic environments are key reservoirs and dissemination pathways of antimicrobial resistance (AMR). However, current water-based surveillance remains fragmented and inefficient for the timely detection of emerging threats. Integrating artificial intelligence with embedded metadata provides a powerful pathway to identify novel antimicrobial resistance genes, characterize resistome profiles, and predict AMR dynamics in real-time by combining omics, environmental, and hydrological data into spatiotemporal predictive models. Successful implementation of this framework will require robust governance, ethical safeguards, and capacity building to support predictive AMR monitoring aligned with the One Health approach.

Antimicrobial resistance (AMR) databases enable the identification of AMR determinants from pathogen sequence data and the prediction of resistance profiles, enhancing AMR surveillance and informing a range of public health interventions. This review compares freely available and regularly updated AMR databases, explores their public health value and highlights key challenges to and opportunities for fully harnessing their potential.

There is a rising concern that temperature increases associated with climate change might select for antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in aquatic ecosystems, although the extent of this phenomenon remains unknown. This study aimed to determine whether increased temperatures induce ARG selection and modify the transcriptional response in a model aquatic ecosystem using an omics approach. River water microcosms were incubated at 20 &#xb0;C, at 28 &#xb0;C (constant temperature increase), and under oscillating temperatures (intervals of 3 days at 20 &#xb0;C and 4 days at 28 &#xb0;C to emulate heatwaves) for 28 days. Both the constantly higher temperature and oscillating temperatures altered bacterial community composition and selected for members carrying ARGs, including two Limnohabitans subpopulations that contain the pmrE polymyxin resistance gene and an Alphaproteobacteria carrying the sul2 sulfonamide resistance gene. In addition, metatranscriptomic analyses revealed a lower abundance (p&#x2009;<&#x2009;0.05) of transcripts related to cell division, bacterial activity/metabolism, antibiotic efflux, stress responses, and cell/gene mobility in samples exposed to oscillating temperatures than in the room temperature controls. This research supports the rising concern that climate change may increase antibiotic resistance in environments exposed to higher temperatures maintained over long periods of time and to repeated short-time heatwave events.