1. Key Laboratory of Medical Molecular Virology, Fudan University Shanghai Medical College, Shanghai, China； 2. Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Abstract：Salmonella enterica serovar Typhimurium encodes two type Ⅲ protein secretion/translocation systems within the pathogenicity island 1 (SPI-1) and island 2 (SPI-2). These translocation systems inject a panel of bacterial effector proteins into host cells to promote bacterial entry into the host cells via the“trigger”mechanism. The translocated effectors exploit the host actin cytoskeleton leading to macropinocytosis and bacteria entry. In this review, we present a workingn model based on recent advances in understanding contributions from individual Salmonella effectors. First, activation of the type Ⅲ secretion system and the delivery of bacterial effector proteins(Ⅰ). Injection of the exchange factor SopE and the inositol polyphosphatase SopB results in the activation of CDC42 and Rac1(Ⅱ), leading to the recruitment of ruffling-associated molecules. SipA and SipC function to lower the critical concentration of actin, stimulating the bundling activity of plastin and stabilizing fibrous actin (F-actin), and nucleating the actin assembly (Ⅲ). SopB promotes membrane fission process by decreasing the local concentration of PIP2 at the base of the membrane ruffles and by recruiting VAMP8 (Ⅳ). The combined activities of these effectors result in a localized and pronounced outward extension of the membrane ruffles, resulting in the engulfment of Salmonella in an enclosed membrane compartment. Salmonella delivers another effector protein, SptP, which reverses the activation of these small G proteins by stimulating their intrinsic GTPase activity and therefore facilitating cell recovery (Ⅴ).
