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Amélie Avet-Rochex

Role of Pseudomonas aeruginosa exoenzyme S in bacterial virulence. A functional study of GAP domain and its targets on immune response in Drosophila melanogaster

Published on 3 October 2005
Thesis presented October 03, 2005

Abstract:
The type III exoenzyme S toxin of Pseudomonas aeruginosa possesses a GAP domain (GTPase Activating Protein) (ExosGAP) inhibiting the Rho GTPases (Rho, Rac and Cdc42) and phagocytosis in Mammal cell lines. We have used a transgenesis approach in Drosop​hila melanogaster using a tissue-specific inducible expression System (UAS-Gal4) to express ExoSGAP. We have demonstrated that ExoSGAP targeted in vivo the Rho GTPases Rho, Racl, Rac2 and Cdc42. The ExoSGAP expression affects fly resistance to infection by inhibiting phagocytosis of bacteria by plasmatocytes, a macrophage cell line, but has no effect on NF-kappaB signaling​ pathways. A genetic approach has allowed the identification of new ExoSGAP targets by looking for genes whose misexpression modifies the eye or wing phenotype induced by the toxin expression. We have identified several genes which can be implicated in JNK and NF-kappaB signaling​ pathways. All these results validate a new strategy to study type III toxins by transgenesis in Drosophila.
In parallel, I have demonstrated GTPase Rac2 specificity in Drosophila resistance to infection. Rac2 participates notably in phagocytosis.
The works of Dr H. Tricoire led to the identification of 180 genes whose misexpression modifies fly response to oxidative stress. We have tested 105 of these lines for their resistance to infections to study a possible correlation between the oxidative and infectious stress response. This screen allows to demonstrate the implication of a protein with a lectin domain called PSLR (Pseudomonas Sensitive Lectin Receptor) in fly immunity.

Keywords:
Innate immune response, Rho GTPases, phagocytosis, NF-kappaB, Drosophila melanogaster, Pseudomonas aeruginosa, Type III secretion system, Exoenzyme S

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