title: Targeting of the actin cytoskeleton during infection by Salmonella strains.
abstract: Many bacterial pathogens produce virulence factors that alter the host cell cytoskeleton to promote infection. Salmonella strains target cellular actin in a carefully orchestrated series of interactions that promote bacterial uptake into host cells and the subsequent proliferation and intercellular spread of the organisms. The Salmonella Pathogenicity Island 1 (SPI1) locus encodes a type III protein secretion system (TTSS) that translocates effector proteins into epithelial cells to promote bacterial invasion through actin cytoskeletal rearrangements. SPI1 effectors interact directly with actin and also alter the cytoskeleton through activation of the regulatory proteins, Cdc42 and Rac, to produce membrane ruffles that engulf the bacteria. SPI1 also restores normal cellular actin dynamics through the action of another effector, SptP. A second TTSS, Salmonella Pathogenecity Island 2 (SPI2), translocates effectors that promote intracellular survival and growth, accompanied by focal actin polymerization around the Salmonella-containing vacuole (SCV). A number of Salmonella strains also carry the spv virulence locus, encoding an ADP-ribosyl transferase, the SpvB protein, which acts later during intracellular infection to depolymerize the actin cytoskeleton. SpvB produces a cytotoxic effect on infected host cells leading to apoptosis. The SpvB effect appears to promote intracellular infection and may facilitate cell-to-cell spread of the organism, thereby enhancing virulence.
authors.affiliation: Department of Medicine 0640, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0640, USA. dguiney@ucsd.edu
authors.forename: Donald G
authors.initials: DG
authors.lastname: Guiney
authors.forename: Marc
authors.initials: M
authors.lastname: Lesnick
mesh_terms: D000199:Actins / Q000502:physiology*; D000818:Animals; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000502:physiology*; D008264:Macrophages / Q000382:microbiology / Q000502:physiology*; D012475:Salmonella / Q000472:pathogenicity*
chemical_list: D000199:Actins