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.
Uchiya
K
K
Howard Hughes Medical Institute and Department of Molecular Microbiology, Washington University School of Medicine, 600 South Euclid Avenue, St Louis, MO 63110-1093, USA.
Barbieri
M A
MA
Funato
K
K
Shah
A H
AH
Stahl
P D
PD
Groisman
E A
EA
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