title: A bacterial type III secretion system inhibits actin polymerization to prevent pore formation in host cell membranes.
abstract: The bacterial pathogen Yersinia pseudotuberculosis uses type III secretion machinery to translocate Yop effector proteins through host cell plasma membranes. A current model suggests that a type III translocation channel is inserted into the plasma membrane, and if Yops are not present to fill the channel, the channel will form a pore. We examined the possibility that Yops act within the host cell to prevent pore formation. Yop- mutants of Y.pseudotuberculosis were assayed for pore-forming activity in HeLa cells. A YopE- mutant exhibited high levels of pore-forming activity. The GTPase-downregulating function of YopE was required to prevent pore formation. YopE+ bacteria had increased pore-forming activity when HeLa cells expressed activated Rho GTPases. Pore formation by YopE- bacteria required actin polymerization. F-actin was concentrated at sites of contact between HeLa cells and YopE- bacteria. The data suggest that localized actin polymerization, triggered by the type III machinery, results in pore formation in cells infected with YopE- bacteria. Thus, translocated YopE inhibits actin polymerization to prevent membane damage to cells infected with wild-type bacteria.
authors.affiliation: Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.
authors.forename: G I
authors.initials: GI
authors.lastname: Viboud
authors.forename: J B
authors.initials: JB
authors.lastname: Bliska
mesh_terms: D000199:Actins / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003546:Cysteine Endopeptidases; D003603:Cytotoxins; D006367:HeLa Cells; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000378:metabolism / Q000472:pathogenicity*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D003603:Cytotoxins; D007473:Ion Channels; C078909:YopB protein, Yersinia; C116117:YopT protein, Yersinia; C063239:yopE protein, Yersinia; D007770:L-Lactate Dehydrogenase; D003546:Cysteine Endopeptidases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein