A Salmonella virulence protein that inhibits cellular trafficking.
Salmonella enterica requires a type III secretion system, designated Spi/Ssa, to survive and proliferate within macrophages. The Spi/Ssa system is encoded within the SPI-2 pathogenicity island and appears to function intracellularly. Here, we establish that the SPI-2-encoded SpiC protein is exported by the Spi/Ssa type III secretion system into the host cell cytosol where it interferes with intracellular trafficking. In J774 macrophages, wild-type Salmonella inhibited fusion of Salmonella-containing phagosomes with lysosomes and endosomes, and interfered with trafficking of vesicles devoid of the microorganism. These inhibitory activities required living Salmonella and a functional spiC gene. Purified SpiC protein inhibited endosome-endosome fusion in vitro. A Sindbis virus expressing the SpiC protein interfered with normal trafficking of the transferrin receptor in vivo. A spiC mutant was attenuated for virulence, suggesting that the ability to interfere with intracellular trafficking is essential for Salmonella pathogenesis.
Howard Hughes Medical Institute and Department of Molecular Microbiology, Washington University School of Medicine, 600 South Euclid Avenue, St Louis, MO 63110-1093, USA.
K
K
Uchiya
M A
MA
Barbieri
K
K
Funato
A H
AH
Shah
P D
PD
Stahl
E A
EA
Groisman
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D002470:Cell Survival; D003600:Cytosol / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial / Q000235:genetics / Q000502:physiology; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism / Q000382:microbiology; D008561:Membrane Fusion; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010588:Phagosomes / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D019779:Salmonella enterica / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence; D020696:rab5 GTP-Binding Proteins
D001426:Bacterial Proteins; D011990:Receptors, Transferrin; C101486:SpiA protein, Salmonella typhimurium; C120280:SpiC protein, Salmonella; D019204:GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins