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MECANISMES DE REGULATION IMPLIQUES DANS LA PATHOGENICITE DE PSEUDOMONAS AERUGINOSA : SYSTEME DE SECRETION DE TYPE III, EPIGENESE ET QUORUM SENSING

Abstract : Pseudomonas aeruginosa is an opportunistic bacterium responsible for severe infections. Its pathogenicity comes from many virulence factors including the type III secretion system (TTSS). This system is activated by contact between the cell and the bacterium or by calcium depletion of the medium and allows injection of toxins into host cell cytosol. Different phenotypes are observed in chronic lung infection: an inducible phenotype by cell contact or calcium depletion and a non inducible one.
If no mutations have occurred, those two phenotypes could be explained by epigenesis.
With the help of a bioinformatic tool, we established all possible dynamics of the minimal TTSS regulatory model which fit the bistability hypothesis and showed the possibility of epigenesis. Through this method, we also design descriminating experiments to validate the hypothesis and first demonstrated the epigenetic acquisition of the capacity for the type III secretion system of P. aeruginosa to be activated by calcium depletion. The possibility of this epigenetic phenotypic switch was then confirmed in vivo in an acute pulmonary infection model.
On an other hand, we showed that TTSS is repressed in high cell density condition. This repression is induced by a signal produced and secreted by P. aeruginosa. Using mutants we demonstrated that known quorum sensing signals are not responsible for this inhibition. Thus, TTSS expression is cell density dependent and is repressed at high cell density by an unknown quorum sensing like mechanism.
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https://tel.archives-ouvertes.fr/tel-00011459
Contributor : Didier Filopon <>
Submitted on : Wednesday, January 25, 2006 - 11:21:49 AM
Last modification on : Friday, November 6, 2020 - 3:48:34 AM
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Didier Filopon. MECANISMES DE REGULATION IMPLIQUES DANS LA PATHOGENICITE DE PSEUDOMONAS AERUGINOSA : SYSTEME DE SECRETION DE TYPE III, EPIGENESE ET QUORUM SENSING. Autre [q-bio.OT]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00011459⟩

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