Article
- The EMBO Journal (1999) 18, 3924 - 3933
- doi:10.1093/emboj/18.14.3924
A Salmonella virulence protein that inhibits cellular trafficking
Kei-ichi Uchiya1, M.Alejandro Barbieri2, Kouichi Funato2, Ankur H. Shah1, Philip D. Stahl2 and Eduardo A. Groisman1
- Howard Hughes Medical Institute and Department of Molecular Microbiology, 600 South Euclid Avenue, St Louis, MO 63110-1093, USA
- Department of Cell Biology and Physiology, Washington University School of Medicine, 600 South Euclid Avenue, St Louis, MO 63110-1093, USA
Correspondence to:
Eduardo A. Groisman, E-mail: groisman@borcim.wustl.edu
Received 26 April 1999; Accepted 24 May 1999; Revised 24 May 1999
Abstract
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.
Keywords:
- endosome,
- intracellular trafficking,
- phagosome,
- Salmonella,
- type III secretion
