Direct nucleation and bundling of actin by the SipC protein of invasive Salmonella.
Salmonella causes severe gastroenteritis in humans, entering non-phagocytic cells to initiate intracellular replication. Bacterial engulfment occurs by macropinocytosis, which is dependent upon nucleation of host cell actin polymerization and condensation ('bundling') of actin filaments into cables. This is stimulated by contact-induced delivery of an array of bacterial effector proteins, including the four Sips (Salmonella invasion proteins). Here we show in vitro that SipC bundles actin filaments independently of host cell components, a previously unknown pathogen activity. Bundling is directed by the SipC N-terminal domain, while additionally the C-terminal domain nucleates actin polymerization, an activity so far known only in eukaryotic proteins. The ability of SipC to cause actin condensation and cytoskeletal rearrangements was confirmed in vivo by microinjection into cultured cells, although as SipC associates with lipid bilayers it is possible that these activities are normally directed from the host cell membrane. The data suggest a novel mechanism by which a pathogen directly modulates the cytoskeletal architecture of mammalian target cells.
Hayward
R D
RD
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Koronakis
V
V
D000199:Actins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites; D001704:Biopolymers / Q000737:chemistry / Q000378:metabolism; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances; D008845:Microinjections; D008854:Microscopy, Electron; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity*; D014774:Virulence
D000199:Actins; D001426:Bacterial Proteins; D001704:Biopolymers; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D011993:Recombinant Fusion Proteins; C094578:Salmonella invasion protein C; D049452:Green Fluorescent Proteins