Uchiya K, Barbieri M A, Funato K, Shah A H, Stahl P D, Groisman E A
Howard Hughes Medical Institute and Department of Molecular Microbiology, Washington University School of Medicine, 600 South Euclid Avenue, St Louis, MO 63110-1093, USA.
EMBO J. 1999 Jul 15;18(14):3924-33. doi: 10.1093/emboj/18.14.3924.
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.
肠炎沙门氏菌需要一种III型分泌系统，即Spi/Ssa，才能在巨噬细胞内存活和增殖。Spi/Ssa系统由SPI-2致病岛编码，似乎在细胞内发挥作用。在此，我们证实SPI-2编码的SpiC蛋白通过Spi/Ssa III型分泌系统输出到宿主细胞胞质溶胶中，在那里它干扰细胞内运输。在J774巨噬细胞中，野生型沙门氏菌抑制含沙门氏菌吞噬体与溶酶体和内体的融合，并干扰不含微生物的囊泡运输。这些抑制活性需要活的沙门氏菌和功能性的spiC基因。纯化的SpiC蛋白在体外抑制内体-内体融合。表达SpiC蛋白的辛德毕斯病毒在体内干扰转铁蛋白受体的正常运输。spiC突变体的毒力减弱，表明干扰细胞内运输的能力对沙门氏菌发病机制至关重要。
