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Premiers mécanismes de régulation d'exlBA, le facteur de virulence des souches de Pseudomonas aeruginosa de type PA7

Abstract : Pseudomonas aeruginosa is an opportunistic pathogen responsible for nosocomial diseases. It provokes infections due to several virulence factors. Among them the most aggressive is the type 3 secretion system (T3SS), associated with severe infection. PA7-like strains, that are taxonomic outliers, lack the T3SS but are still pathogenic thanks to the novel virulence system ExlBA. This T5bSS, or TPS, is composed by the transporter ExlB that allows translocation of ExlA toxin to induce permeabilisation of eukaryotic cell membrane.This study is the first investigation of regulatory mechanisms that modulate ExlBA. It provided evidence that iron depletion is an activator signal of exlBA gene expression. Furthermore, the two main second messengers, cAMP and c-di-GMP, are involved in ExlBA regulation. CyaB-cAMP/Vfr pathway, known to regulate T3SS, controls toxicity of PA7-like strains through direct transcriptional activation of exlBA. This pathway may be stimulated by an extracellular calcium chelation. At the same time, while ExlA was supposed to be secreted to kill eukaryotic cells, this work showed that the toxin must be exposed at the surface of the bacterial membrane to cause lysis of these cells, by a mechanism dependent on c-di-GMP. Indeed, a c-di-GMP high concentration prevents ExlA secretion by inducing its maintenance at the ExlB transporter, that would promote the action of the toxin on eukaryotic membranes.
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Submitted on : Wednesday, November 6, 2019 - 4:26:18 PM
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  • HAL Id : tel-02352034, version 1



Alice Berry. Premiers mécanismes de régulation d'exlBA, le facteur de virulence des souches de Pseudomonas aeruginosa de type PA7. Médecine humaine et pathologie. Université Grenoble Alpes, 2019. Français. ⟨NNT : 2019GREAV015⟩. ⟨tel-02352034⟩



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