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Génomique épidémiologique de Salmonella

Abstract : Over a century has passed since the discovery of Salmonella and yet, this pathogen still intrigues researchers. Its ability to withstand many antibiotics is of increasing concern. The monitoring of this pathogen is based on a rapid and discriminatory typing to identify the sources of contaminated food as early as possible. The conventional methods are long, heavy and non-automatable. Understanding the emergence and evolution of Salmonella is the key to eradicate this pathogen, which has remained one of the leading causes of foodborne bacterial diarrhea in the world. During the last decades, spectacular progress has been made in the world of microbiology with the arrival of workbench sequencers, passing from a dozen to hundreds of millions of sequences processed. Facilitated access to numerous genome sequences and dedicated tools are mandatory. Tools currently available are not sufficiently discriminating for the subtype of S. enterica serotype Typhimurium, a predominant serotype of Salmonella. Throughout this study, we showed the interest of whole genome sequencing, a multidisciplinary tool, for the genomic study of Salmonella. (1) After sequencing over 300 S. enterica serotype Typhimurium genomes, we have developed an in silico subtyping tool for this serotype, based on the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) polymorphism. High-throughput microbiological monitoring of salmonellosis has been routinely validated on over 800 genomes. The study of coevolution between the chromosome (SNPs of the core genome) and the two CRISPR regions made it possible to establish a nomenclature defining the different populations of this serotype. (2) Genomic analysis of 280 historical strains of S. enterica serotype Typhimurium showed that plasmids carrying beta-lactamase genes, which confer resistance to ampicillin, were widespread within this serotype in the late 1950s, years before ampicillin was first used for clinical purposes. The presence of penicillin G in the farming environment where these compounds were used as growth promoters, may have led to the selection of the first ampicillin-resistant strains. (3) The phylogenetic study of a genome from the corpse of a young woman who died over 800 years ago, probably due to enteric fever, and 219 historical and recent genomes of the serotypes Paratyphi C, Choleraesuis and Typhisuis have shown, despite the differences in host specificity, that their genomes were very similar over the past 4000 years. Thus, the combination of genotypic and phylogenetic approaches has increased our knowledge of the evolution of this pathogen.Key words: Whole genome sequencing, epidemiological monitoring, CRISPR, SNP, antibiotic resistance, phylogeny, evolution
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Alicia Tran Dien. Génomique épidémiologique de Salmonella. Médecine humaine et pathologie. Institut agronomique, vétérinaire et forestier de France, 2018. Français. ⟨NNT : 2018IAVF0001⟩. ⟨tel-02006644⟩

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