title: Suppression of Drosophila cellular immunity by directed expression of the ExoS toxin GAP domain of Pseudomonas aeruginosa.
abstract: We show here that transgenic Drosophila can be used to decipher the effect of a bacterial toxin on innate immunity and demonstrate the contribution of blood cells in fly resistance to bacterial infection. ExoS is a Pseudomonas aeruginosa exotoxin directly translocated into the host cell cytoplasm through the type III secretion system found in many Gram-negative bacteria. It contains a N-terminal GTPase activating (GAP) domain that prevents cytoskeleton reorganization by Rho family of GTPases in cell culture. Directed expression of the ExoS GAP domain (ExoSGAP) during fly eye morphogenesis inhibited Rac1-, Cdc42- and Rho-dependent signalling, demonstrating for the first time its activity on RhoGTPases in a whole organism. We further showed that fly resistance to P. aeruginosa infections was altered when ExoSGAP was expressed either ubiquitously or in haemocytes, but not when expressed into the fat body, the major source of NF-(kappa)B-dependent anti-microbial peptide synthesis. Fly sensitivity to infection was also observed with Gram-positive Staphylococcus aureus strain and was associated to a reduced phagocytosis capacity of ExoSGAP-expressing haemocytes. Our results highlight the major contribution of cellular immunity during the first hours after Drosophila infection by P. aeruginosa, an opportunist pathogen affecting patients with pathologies associated to a reduced leukocyte number.
authors.affiliation: CEA-Grenoble, Département de Réponse et Dynamique Cellulaires, UMR5092 CEA/CNRS/UJF, 17, rue des Martyrs 38054 Grenoble cedex 9, France.
authors.forename: Amelie
authors.initials: A
authors.lastname: Avet-Rochex
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bergeret
authors.forename: Ina
authors.initials: I
authors.lastname: Attree
authors.forename: Marie
authors.initials: M
authors.lastname: Meister
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Fauvarque
mesh_terms: D036002:ADP Ribose Transferases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D001427:Bacterial Toxins / Q000096:biosynthesis* / Q000235:genetics; D004331:Drosophila melanogaster / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D005123:Eye / Q000254:growth & development; D005216:Fat Body / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics; D006434:Hemocytes / Q000378:metabolism; D008855:Microscopy, Electron, Scanning; D009024:Morphogenesis; D010587:Phagocytosis; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000472:pathogenicity; D014774:Virulence; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D020690:GTPase-Activating Proteins; D036002:ADP Ribose Transferases; C444820:exoenzyme S; D020741:rho GTP-Binding Proteins