23/01-2023 - Vincent DERUELLE : ExoU and ExoY, two toxins from Pseudomonas aeruginosa with different mechanisms of action and biological effects

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 13h–14h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 23 JANVIER 2023

ExoU and ExoY, two toxins from Pseudomonas aeruginosa with different mechanisms of action and biological effects

Vincent DERUELLE

Post-doctorant - Institut Pasteur, Unité de Biochimie des Interactions Macromoléculaires, Département de Biologie Structurale et Chimie

invité par Equipe de Harriet CORVOL (Equipe CORVOL (gabrielle.dupuis@inserm.fr))

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The Gram-negative bacterium Pseudomonas aeruginosa is at the top of the WHO's list of pathogens for which there is a need to develop and discover new therapeutic approaches. In humans, it is an opportunistic pathogen that frequently colonizes hospitalized patients with compromised host defenses, leading to acute or chronic life-threatening infections. This ability to cause deadly pathologies is promoted by a broad panel of virulence factors. Among them, the Type III Secretion System (T3SS) plays an important role in acute infections. It is a syringe-like apparatus that pierces the host cell membrane and allows the delivery of four toxins directly into the host cytoplasm. These toxins, named ExoS, ExoT, ExoU and ExoY are first inactive when injected and require a different cell cofactor to be activated and to hijack cellular pathways. However, several aspects of their mechanism of action upon injection remain elusive. Here, I will speak about the necrotizing toxin ExoU and the nucleotidyl cyclase ExoY for which the trafficking in human cells and the role in the pathogenicity of P. aeruginosa are still not well defined, respectively. Several approaches have been used to answer these questions, such as the CRISPR-Cas9, modification of P. aeruginosa genome or the creation of stable cell lines to detect cAMP and cGMP production. We hope that these fundamental results will eventually lead to the discovery of new therapeutic targets to fight against infections by P. aeruginosa strains.

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