title: Rafts can trigger contact-mediated secretion of bacterial effectors via a lipid-based mechanism.
abstract: Infection by the Gram-negative bacterial pathogen Shigella flexneri depends on its ability to invade host cells. Bacterial engulfment requires a functional type III secretion system (TTSS) allowing the translocation into host cells of bacterial effectors that activate cell-signaling cascades. We demonstrated previously that specialized lipid membrane domains enriched in cholesterol and sphingolipids (rafts) are involved during early steps of invasion, namely in binding and host cell entry. In this study, we addressed the issue of contact-mediated secretion by the TTSS. We show that contact-mediated and TTSS-induced hemolysis depend on the presence of cholesterol on the host cell surface. We found that purified detergent resistant membranes were able to activate TTSS. Finally, we found that artificial liposomes, devoid of proteins, were able to activate the TTSS but only when their composition mimicked that of lipid rafts. Altogether, these data indicate that specific lipid packing can trigger contact-mediated secretion by S. flexneri.
authors.affiliation: Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, CH1211 Genève 4, Switzerland.
authors.forename: Françoise G
authors.initials: FG
authors.lastname: van der Goot
authors.forename: Guy
authors.initials: G
authors.lastname: Tran van Nhieu
authors.forename: Abdelmounaaïm
authors.initials: A
authors.lastname: Allaoui
authors.forename: Phillipe
authors.initials: P
authors.lastname: Sansonetti
authors.forename: Frank
authors.initials: F
authors.lastname: Lafont
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D003902:Detergents / Q000737:chemistry; D005089:Exocytosis / Q000502:physiology*; D006461:Hemolysis; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D012763:Shigella flexneri / Q000378:metabolism / Q000472:pathogenicity*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D001426:Bacterial Proteins; D003902:Detergents; D008081:Liposomes; C087447:ipaB protein, Shigella; D002784:Cholesterol