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Diversité, complexité et adaptation au comportement pathogène au sein du genre Aeromonas

Abstract : Aeromonas groups ubiquitous bacteria mainly living in aquatic environments. These opportunistic pathogens for human and numerous animals have a large repertoire of virulence-associated factors. Although pathotypes were proposed and despite some species are more frequently isolated in human and animal infections, their pathogenicity is still poorly understood, mostly because very few comprehensive functional studies are available and because investigations taking into account the genetic diversity and the biological complexity within the genus are lacking.We assumed that for an opportunistic bacterial pathogen of environmental origin as versatile and ubiquitous as Aeromonas, the population structure in complex of species, the outstanding genetic/genomic diversity, the polymorphism of virulence factors and the interactions within pathogenic populations can act as factors driving the adaptation to a pathogenic behaviour. To test this hypothesis, we studied i) the diversification within “A. media”, a complex of species used as a model by a population study that included multilocus genetics, phylogenetics, evolutionary features, comparative genomics, as well as phenotypics, lifestyle and habitat ii) the patho-genomics of well-known virulence factors in aeromonads (aerolysin, thermolabile and thermostable enterotoxins, exotoxin A, serine protease, components and effectors of type III secretion system, and lateral flagellin) in a population that is representative of the known taxonomic diversity in the genus (30 species) and iii) the pathogenic behaviour using an in vivo model (Caenorhabditis elegans), an in vitro model (cytotoxicity, cytoadhesion, biofilm production, motility), and intercellular signals production (type I quorum-sensing) for populations involved in mixed aeromonosis, i.e. 5% of human aeromonosis defined by the isolation of at least 2 distinct clones.The phenomenon of speciation described in the complex “A. media” that aggregates 3 genomic species demonstrates that Aeromonas harbours a population structured in complexes of closely related species whose genetic and genomic diversity, as well as evolution mode (mutations and recombinations) reveal a wide adaptative and patho-adaptative potential linked to lineage emergence. Among the complex “A. media”, the species A. rivipollensis seems to be more adapted to a host-associated lifestyle and harbours specific genes for the resistance to environmental stress. Aeromonas has a wide range of virulence-associated genes, which presented diverse evolutive history. Some of them display a phylogeny linked to the core-genome evolution. These results suggest that these genes are involved in speciation processes probably related to niches adaptation. The evaluation of performances of virulence PCRs revealed major lacks of sensitivity of tested methods mainly due to the genetic polymorphism of the virulence factors. By using in vivo models and in vitro models, we also showed that Aeromonas mixed populations recovered from clinical samples could change the course of infection, likely through a cooperative or competitive mechanism that involves cell-to-cell signalling.The high complexity of Aeromonas results from its population structure, virulence factors polymorphism and multicellular behaviours. They are all putative adaptation factors to a pathogenic behaviour that may explain at least partially the difficulties encountered to elucidate pathogenicity of these bacteria.
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Emilie Talagrand. Diversité, complexité et adaptation au comportement pathogène au sein du genre Aeromonas. Sciences agricoles. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTT123⟩. ⟨tel-01704514⟩

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