Bacteria-generated PtdIns(3) P recruits VAMP8 to facilitate phagocytosis

Abstract

Salmonella enterica serovar Typhimurium invades non-phagocytic cells by inducing macropinocytosis. SopB is involved in modulating actin dynamics to promote Salmonella -induced invasion. We report here that SopB-generated PtdIns(3) P binds VAMP8/endobrevin to promote efficient bacterial phagocytosis. VAMP8 is recruited to Salmonella -induced macropinosomes in a nocodazole-dependent, but Brefeldin A-independent, manner. We found that VAMP8 directly binds to and colocalizes with PtdIns(3) P. The inositol phosphatase activity of SopB is required for PtdIns(3) P and VAMP8 accumulation, while wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, has no effect. Knockdown of endogenous VAMP8 by small interfering RNA or expression of a truncated VAMP8 (1-79aa) reduces the invasion level of wild-type Salmonella to that of the phosphatase-deficient SopB C460S mutant. Our study demonstrates that Salmonella exploit host SNARE proteins and vesicle trafficking to promote bacterial entry. © 2007 The Author Journal compilation © 2007 Blackwell Publishing Ltd.