A Salmonella virulence protein that inhibits cellular trafficking

Salmonella enterica requires a type III secretion system, designated Spi/Ss a, to survive and proliferate within macrophages. The Spi/Ssa system is enc oded within the SPI-2 pathogenicity island and appears to function intracel lularly. 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-typ e Salmonella inhibited fusion of Salmonella-containing phagosomes with lyso somes and endosomes, and interfered with trafficking of vesicles devoid of the microorganism, These inhibitory activities required living Salmonella a nd a functional spiC gene, Purified SpiC protein inhibited endosome-endosom e fusion in vitro, A Sindbis virus expressing the SpiC protein interfered w ith normal trafficking of the transferrin receptor in vivo. A spiC mutant w as attenuated for virulence, suggesting that the ability to interfere with intracellular trafficking is essential for Salmonella pathogenesis.