Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection
Esterification of cholesterol by a type III secretion effector during intracellular Salmonella infection
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DOI：
10.1111/j.1365-2958.2008.06142.x
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发表时间：
2008-04-01
影响因子：
3.6
通讯作者：
Haldar, Kasturi
中科院分区：
文献类型：
--
作者：
Nawabi, Parwez;Catron, Drew M.;Haldar, Kasturi
鼠伤寒沙门氏菌在宿主细胞内的液泡中存活依赖于由沙门氏菌致病岛2（SPI - 2）编码的分泌型毒力因子。在含沙门氏菌的液泡（SCV）中检测到高水平的胆固醇。在此我们表明，SPI - 2效应蛋白SseJ在体外、细胞内以及感染过程中可使胆固醇酯化。与ΔsseJ细菌相比，野生型细菌的细胞内感染导致HeLa细胞和RAW巨噬细胞中胆固醇酯产生水平更高，并且显示可增加脂滴（富含胆固醇酯的结构）的水平。SseJ的异位表达降低了细胞膜中的胆固醇水平，并拮抗了第二种已知对SCV稳定性很重要的细菌效应蛋白的主要膜活性。先前在感染小鼠模型中的研究已确定了ΔsseJ细菌的毒力缺陷，并表明SseJ在调节SCV动态方面起作用。我们表明SseJ分子活性的数据提示，胆固醇及其在SCV中的酯化作用对细胞内细菌的存活具有重要功能。
Survival of Salmonella typhimurium within a vacuole in host cells depends on secreted virulence factors encoded by the Salmonella pathogenicity island 2 (SPI-2). High levels of cholesterol are detected at the Salmonella-containing vacuole (SCV). Here we show that the SPI-2 effector SseJ esterifies cholesterol in vitro, in cells and during infection. Intracellular infections with wild-type as compared with Delta sseJ bacteria led to higher levels of cholesterol ester production in HeLa cells and RAW macrophages and were shown to increase levels of lipid droplets (structures enriched in cholesterol esters). Ectopic expression of SseJ reduced cholesterol levels in cellular membranes and antagonized a major membrane activity of a second bacterial effector known to be important to the stability of the SCV. Previous studies in mouse models of infection have established a virulence defect in Delta sseJ bacteria and have suggested a role for SseJ in regulating SCV dynamics. Our data indicating the molecular activity of SseJ suggest that cholesterol and its esterification at the SCV are functionally important for intracellular bacterial survival.