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Madec, J.-Y.

Publications and source records attributed to Madec, J.-Y..

6 recordsLinked to original sources

The interplay between Mobilome and Resistome in Staphylococcus aureus

Antibiotic resistance genes (ARGs) in Staphylococcus aureus can disseminate vertically through successful clones, but also horizontally through the transfer of genes conveyed by mobile genetic elements (MGEs). The underexplored MGE/ARG associations in S. aureus favor the emergence of multidrug-resistant clones, posing a significant threat to human and animal health. This study investigated the interplay between the mobilome, encompassing MGEs, and the resistome, the collection of ARGs, in more than 10,000 S. aureus genomes from human and animal sources. The analysis revealed a remarkable diversity of MGEs and ARGs, with plasmids and transposons being the main carriers of resistance genes. Numerous MGE/ARG associations were identified, suggesting that MGEs play a critical role in the dissemination of resistance. A high degree of similaritywas observed in MGE/ARG associations between human and animal isolates, highlighting the potential for unrestricted spread of ARGs between hosts. While clonal expansion is a major driver of resistance dissemination in S. aureus, our results showed that MGEs and their associated ARGs can spread across different strain types (STs), favoring the evolution of these clones and their adaptation in selective environments. The high variability of MGE/ARG associations within individual STs and the ir spread across several STs highlight the crucial role of MGEs in shaping the S. aureus resistome. Overall, this study provides valuable insights into the complex interplay between MGEs and ARGs in S. aureus, emphasizing the need to elucidate the mechanisms governing the epidemic success of MGEs, particularly those implicated in ARG transfer. ImportanceThe research presented in this article highlights the crucial importance of understanding the interactions between mobile genetic elements (MGEs) and antibiotic resistance genes (ARGs) carried by Staphylococcus aureus, a versatile bacterium that can be both a harmless commensal and a dangerous pathogen for humans and animals. S. aureus strains represent a major threat due to their ability to rapidly acquire and disseminate ARGs. By analyzing a large dataset of S. aureus genomes, we highlighted the substantial role of MGEs, in particular plasmids and transposons, in the dissemination of ARGs within and between S. aureus populations, bypassing the host barrier. Given that multidrug-resistant S. aureus strains are classified as a high-prioritypathogenby global health organizations, this knowledge is crucial for understanding the complex dynamics of transmission of antibiotic resistance in this species.

microbiology↗

Interplay between bacterial clone and plasmid in the spread of antibiotic resistance genes in the gut: lessons from a temporal study in veal calves

Intestinal carriage of extended spectrum {beta}-lactamase (ESBL)-producing Escherichia coli is a frequent, increasing and worrying phenomenon, but little is known about the molecular scenario and the evolutionary forces at play. We screened 45 veal calves, known to have high prevalence of carriage, for ESBL-producing E. coli on 514 rectal swabs (one randomly selected colony per sample) collected over six months. We characterized the bacterial clones and plasmids carrying blaESBL genes with a combination of genotyping methods, whole genome sequencing and conjugation assays. One hundred and seventy-three ESBL-producing E. coli isolates [blaCTX-M-1 (64.7%), blaCTX-M-14 (33.5%) or blaCTX-M-15 (1.8%)] were detected, belonging to 32 bacterial clones, mostly of phylogroup A. Calves were colonized successively by different clones with a trend in decreasing carriage. The persistence of a clone in a farm was significantly associated with the number of calves colonized. Despite a high diversity of E. coli clones and blaCTX-M-carrying plasmids, few blaCTX-M gene/plasmid/chromosomal background combinations dominated, due to (i) efficient colonization of bacterial clones and/or (ii) successful plasmid spread in various bacterial clones. The scenario clone vs. plasmid spread depended on the farm. Thus, epistatic interactions between resistance genes, plasmids and bacterial clones contribute to optimize fitness in specific environments.

microbiology↗

OASIS evaluation of the French surveillance network for antimicrobial resistance in diseased animals (RESAPATH): success factors at the basis of a well-performing volunteer system

Antimicrobial resistance is a One Health issue requiring the development of surveillance systems in the human, environmental and animal sectors. In Europe, the surveillance of antimicrobial resistance on zoonotic pathogens and indicator bacteria in healthy food-producing animals has been implemented on a legal basis, while countries are also expected to extend their surveillance to diseased animals in the frame of national action plans. In this context, evaluating existing antimicrobial resistance surveillance systems in veterinary medicine is important to improve systems in place, but also to help other countries learn from these experiences, understand success factors and anticipate challenges. With this aim, the French surveillance network for antimicrobial resistance in bacteria from diseased animals (RESAPATH) was evaluated using the OASIS assessment tool. Key performance factors included (i) a strong and inclusive central institutional organization defining clear and well-accepted surveillance objectives, scope and procedures, (ii) strong skills in epidemiology and microbiology and (iii) a win-win approach enabling the volunteer participation of 71 field laboratories and where a free annual proficiency testing plays a pivotal role. The main area of improvement of RESAPATH was its time-consuming data management system.

microbiology↗

Defining the scope of the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet): a bottom-up and One Health approach

BackgroundBuilding the European Antimicrobial Resistance Surveillance network in Veterinary medicine (EARS-Vet) was proposed to strengthen the European One Health antimicrobial resistance (AMR) surveillance approach. ObjectivesThe objectives were to (i) define the combinations of animal species, production types, age categories, bacterial species, specimens and antimicrobials to be monitored in EARS-Vet and to (ii) determine antimicrobial test panels able to cover most combinations. MethodsThe EARS-Vet scope was defined by consensus between 26 European experts. Decisions were guided by a survey of the combinations that are relevant and feasible to monitor in diseased animals in 13 European countries (bottom-up approach). Experts also considered the One Health approach and the need for EARS-Vet to complement existing European AMR monitoring systems coordinated by the European Centre for Disease Prevention and Control (ECDC) and the European Food Safety Authority (EFSA). ResultsEARS-Vet would monitor AMR in six animal species (cattle, swine, chicken (broiler and laying hen), turkey, cat and dog), for 11 bacterial species (Escherichia coli, Klebsiella pneumoniae, Mannheimia haemolytica, Pasteurella multocida, Actinobacillus pleuropneumoniae, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus hyicus, Streptococcus uberis, Streptococcus dysgalactiae and Streptococcus suis). Relevant antimicrobials for their treatment were selected (e.g. tetracyclines) and complemented with antimicrobials of more specific public health interest (e.g. carbapenems). Three test panels of antimicrobials were proposed covering most EARS-Vet combinations of relevance for veterinary antimicrobial stewardship. ConclusionsWith this scope, EARS-Vet would enable to better address animal health in the strategy to mitigate AMR and better understand the multi-sectoral AMR epidemiology in Europe.

microbiology↗

Drivers of ESBL-producing Escherichia coli dynamics in calf fattening farms: a modelling study

The contribution of bacteria in livestock to the global burden of antimicrobial resistance raises concerns worldwide. However, the dynamics of selection and diffusion of antimicrobial resistance in farm animals are not fully understood. Here, we used veal calf fattening farms as a model system, as they are a known reservoir of Extended Spectrum {beta}-Lactamase-producing Escherichia coli (ESBL-EC). Longitudinal data of ESBL-EC carriage and antimicrobial use (AMU) were collected from three veal calf farms during the entire fattening process. We developed 18 agent-based mechanistic models to assess different hypotheses regarding the main drivers of ESBL-EC dynamics in calves. The models were independently fitted to the longitudinal data using Markov Chain Monte Carlo and the best model was selected. Within-farm transmission between individuals and sporadic events of contamination were found to drive ESBL-EC dynamics on farms. In the absence of AMU, the median carriage duration of ESBL-EC was estimated to be 19.6 days (95% credible interval: [12.7; 33.3]). In the best model, AMU was found to influence ESBL-EC dynamics, by affecting ESBL-EC clearance rather than acquisition. This effect of AMU was estimated to decrease gradually after the end of exposure and to disappear after 62.5 days [50.0; 76.9]. Moreover, using a simulation study, we quantified the efficacy of ESBL-EC mitigation strategies. Decreasing ESBL-EC prevalence by 50% on arrival at the fattening farm reduced prevalence at slaughter age by 33.3%. Completely eliminating the use of selective antibiotics had a strong effect on average ESBL-EC prevalence (relative reduction of 79.6%), but the effect was mild if this use was only decreased by 50% compared to baseline (relative reduction of 3.7%).

microbiology↗

Stepwise evolution and convergent recombination underlie the global dissemination of carbapenemase-producing Escherichia coli

Carbapenem-resistant Enterobacteriaceae are considered by WHO as \"critical\" priority pathogens for which novel antibiotics are urgently needed. The dissemination of carbapenemase-producing Escherichia coli (CP-Ec) in the community is a major public health concern. However, the global molecular epidemiology of CP-Ec isolates, as well as the genetic bases for the emergence and global dissemination of specific lineages, remain largely unknown. Here, by combining a thorough genomic and evolutionary analysis of Ec ST410 isolates with a broad analysis of 12,584 E. coli and Shigella genomes, we showed that the fixation of carbapenemase genes depends largely on a combination of mutations in ftsI encoding the penicillin binding protein 3 and in the porin genes ompC and ompF. Mutated ftsI genes and a specific ompC allele inducing reduced susceptibility to diverse {beta}-lactams spread across the species by recombination. The selection of CP-Ec lineages able to disseminate is more complex than the mere acquisition of carbapenemase genes.

microbiology↗