Analysis of the T3SS1-dependent cytotoxicity of Vibrio parahaemolyticus

副溶血性弧菌是一种主要的食源性致病菌，其细胞毒性依赖于其III型分泌系统(T3SS1)。虽然T3SS1效应器VEPA在细胞毒性中起主要作用，但其机制尚不清楚。在本研究中，酵母全基因组筛选显示，V-ATPase的c亚基对VEPA的毒性是不可或缺的。生化亚细胞分级分析表明，VEPA可能与感染细胞中的溶酶体有关。虽然VEPA的毒性与V-ATPase的功能无关，但VEPA可诱导溶酶体膜通透性和溶酶体内容物的外漏。因此，这些数据表明，T3SS1效应物VEPA靶向V-ATPase的c亚基，并诱导宿主细胞溶酶体破裂和随后的细胞死亡。

Vibrio parahaemolyticus, a major food-borne pathogen, exhibits cytotoxicity that is dependent on its type III secretion system (T3SS1). Although a T3SS1 effector VepA plays a major role in the cytotoxicity, the mechanism was unknown.In this study, a yeast genome-wide screen revealed that subunit c of V-ATPase is indispensable for the toxicity of VepA. Biochemical subcellular fractionation showed that VepA may be associated with lysosomes in infected cells. Although the toxicity of VepA was independent of the function of V-ATPases, VepA induces lysosomal membrane permeabilization and the leakage of contents from lysosomes. Therefore, these data suggest that the T3SS1 effector VepA targets subunit c of V-ATPase and induces the rupture of host cell lysosomes and subsequent cell death.