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Etude des premières étapes de la transformation naturelle chez Helicobacter pylori

Abstract : H. pylori is a Gram negative flagellar bacterium that colonizes nearly 50% of the world population. Infection is generally asymptotic but can evolve to ulcerous gastritis (15% of the cases) or stomach cancer (1% of the cases). H. pylori infection is usually treated with antibiotic but the last years saw a dramatic increase in the number of resistant strains. This increase, and the high prevalence of H. pylori, are probably caused by its huge genetic variability likely due to a strong mutagenesis rate associated with efficient recombination and horizontal gene transfer. H. pylori is indeed naturally competent for transformation which is the biological process allowing capture, internalization and integration of exogenous DNA in the genome of a bacterium. This process promotes genetic diversity in a population and could permit rapid adaptation to environmental changes. During my thesis, I participated to the development of a method to visualize transformation in H. pylori living cells. Using fluorescently labelled DNA, this method allowed us for the first time to follow directly the entry of a transforming DNA into the cytoplasm of competent bacteria. It also allowed us to confirm the role of the ComEC protein in the internalization of the DNA in the cytoplasm. The work I performed also allowed to show that the level of expression of the uptake complex determines the transformation efficiency of H. pylori. The amount of captured DNA would then be a limiting factor for the transformation in this bacterium. Finally, I initiated the biochemical and genetic characterization of the NucT protein, a nuclease associated to the membrane and implicated in the transformation.
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Christopher Corbinais. Etude des premières étapes de la transformation naturelle chez Helicobacter pylori. Microbiologie et Parasitologie. Université Pierre et Marie Curie - Paris VI, 2015. Français. ⟨NNT : 2015PA066620⟩. ⟨tel-01655503⟩

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