Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function
Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function
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DOI：
10.1111/j.1462-5822.2006.00762.x
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发表时间：
2006-12-01
影响因子：
3.4
通讯作者：
Finlay, B. Brett
中科院分区：
文献类型：
--
作者：
Boyle, Erin C.;Brown, Nat F.;Finlay, B. Brett
鼠伤寒沙门氏菌是引起人类胃肠炎的主要原因之一。鼠伤寒沙门氏菌感染上皮单层破坏了正常维持肠道屏障和调节细胞极性的紧密连接。紧密连接的破坏取决于沙门氏菌致病性岛-1(SPI-1)3型分泌系统，但涉及的特定效应因子尚未确定。在这项研究中，我们证明了SopB、SopE、SopE2和SipA是SPI-1分泌的效应因子，负责破坏紧密连接的结构和功能。鼠伤寒沙门氏菌可以通过抑制宿主蛋白的香叶化来阻止紧密连接的破坏，但不依赖宿主蛋白的合成或宿主衍生产物的分泌。与野生型鼠伤寒沙门氏菌、Delta SopB、Delta Sope/E2、Delta Sipa或Delta SipA/SopB突变体不同，Delta SopB/E/E2和Delta SipA/Sope/E2突变体不能增加极化上皮单层的通透性，不破坏ZO-1和occludin的分布或水平，也不改变细胞的极性。这些数据表明，SPI-1分泌的效应物利用其刺激Rho家族GTP酶的能力来破坏紧密连接的结构和功能。
Salmonella enterica serovar Typhimurium is a major cause of human gastroenteritis. Infection of epithelial monolayers by S. Typhimurium disrupts tight junctions that normally maintain the intestinal barrier and regulate cell polarity. Tight junction disruption is dependent upon the Salmonella pathogenicity island-1 (SPI-1) type 3 secretion system but the specific effectors involved have not been identified. In this study we demonstrate that SopB, SopE, SopE2 and SipA are the SPI-1-secreted effectors responsible for disruption of tight junction structure and function. Tight junction disruption by S. Typhimurium was prevented by inhibiting host protein geranylgeranylation but was not dependent on host protein synthesis or secretion of host-derived products. Unlike wild-type S. Typhimurium, Delta sopB, Delta sopE/E2, Delta sipA, or Delta sipA/sopB mutants, Delta sopB/E/E2 and Delta sipA/sopE/E2 mutants were unable to increase the permeability of polarized epithelial monolayers, did not disrupt the distribution or levels of ZO-1 and occludin, and did not alter cell polarity. These data suggest that SPI-1secreted effectors utilize their ability to stimulate Rho family GTPases to disrupt tight junction structure and function.