沙门菌侵袭研究进展

摘要

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 working 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 Racl (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).%鼠伤寒沙门菌表达两个不同的Ⅲ型分泌系统(typeⅢsecretion/translocation systems,TTSS),分别由致病岛1和2(pathogenicity islands 1 and 2,SPI-1 and SPI-2)编码.细菌依赖TTSS将效应蛋白转运至宿主细胞,通过"触发"机制诱导细菌进入宿主细胞.这些效应蛋白可诱导细胞骨架重排,导致"巨吞饮",促使细菌入侵.本综述依据多种沙门菌效应蛋白的功能,建立沙门菌侵袭模型.TTSS活化并转运效应蛋白进入宿主细胞发挥功能(Ⅰ).小G蛋白交换因子SopE和肌醇磷酸酯酶SopB通过激活CDC42和Racl,诱导内陷相关的蛋白聚集(Ⅱ).SipA和SipC通过降低肌动蛋白临界浓度、刺激网素成柬、稳定纤维状肌动蛋白(fibrousactin,F-actin)以及使肌动蛋白核化等功能,促使细菌入侵(Ⅲ).SopB可使膜内陷区PIP2的浓度降低以及VAMP8聚集,促使细胞膜分裂(Ⅳ).这些效应蛋白的联合作用,使膜皱褶在局部向外显著延伸,使沙门菌被细胞内形成的特殊膜结构包裹.沙门菌的另一种效应蛋白SptP,通过刺激小G蛋白内源性GTPase的活性,抑制小G蛋白的活化,使细胞膜恢复至原有状态(Ⅴ).