Cooperation of Salmonella pathogenicity islands 1 and 4 is required to breach epithelial barriers
Cooperation of Salmonella pathogenicity islands 1 and 4 is required to breach epithelial barriers
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DOI：
10.1111/j.1462-5822.2008.01218.x
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发表时间：
2008-11-01
影响因子：
3.4
通讯作者：
Hensel, Michael
中科院分区：
文献类型：
--
作者：
Gerlach, Roman G.;Claudio, Nuno;Hensel, Michael
侵袭是克服极化上皮细胞形成屏障的重要微生物毒力策略。肠沙门氏菌是一种食源性病原体，它部署一种III型分泌系统来操纵肌动蛋白细胞骨架，并触发内化到上皮细胞。在这里，我们表明这一功能不足以进入极化细胞，并报告了从管腔一侧穿透上皮需要第III型分泌系统和沙门氏菌致病岛4赋予的新的毒力功能。沙门氏菌致病岛4编码了巨大的非菌毛粘附素SiiE的I型分泌系统，该系统介导沙门氏菌与顶膜上的微绒毛的亲密接触。缺乏SiIE的突变株不能入侵极化细胞，破坏上皮屏障功能，也不能消除根尖刷状边界。对SIIE中重复结构域的缺失分析表明，粘附素的大小具有重要的功能。我们的观察表明，要有效地穿透上皮屏障，需要编码不同分泌系统的两个沙门氏菌致病岛的协同活动。这些发现强调了上皮刷子边界的作用，并揭示了细菌病原体用来克服这一障碍的新机制。
Invasion is an important microbial virulence strategy to overcome the barrier formed by polarized epithelial cells. Salmonella enterica is a food-borne pathogen that deploys a type III secretion system for the manipulation of the actin cytoskeleton and to trigger internalization into epithelial cells. Here we show that this function is not sufficient to enter polarized cells and report that penetration of epithelia from the luminal side requires both the type III secretion system and novel virulence functions conferred by Salmonella pathogenicity island 4. Salmonella pathogenicity island 4 encodes a type I secretion system for the giant non-fimbrial adhesin SiiE that mediates intimate contact of Salmonella to microvilli on the apical membrane. Mutant strains lacking SiiE fail to invade polarized cells, to destroy epithelial barrier functions and to efface the apical brush border. Deletion analyses of repetitive domains in SiiE indicate that the large size of the adhesin is of functional importance. Our observations demonstrate that efficient penetration of epithelial barriers requires the cooperative activity of two Salmonella pathogenicity islands encoding different secretion systems. These findings underline the role of the epithelial brush border and reveal a new mechanism used by bacterial pathogens to overcome this barrier.