A bacterial type III secretion system inhibits actin polymerization to prevent pore formation in host cell membranes.
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.
Viboud
G I
GI
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.
Bliska
J B
JB
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
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