Functional Type 1 Secretion System Involved in Legionella pneumophila Virulence
Functional Type 1 Secretion System Involved in Legionella pneumophila Virulence
复制标题
DOI：
10.1128/jb.02164-14
复制
发表时间：
2015-02-01
影响因子：
3.2
通讯作者：
Gilbert, Christophe
中科院分区：
文献类型：
--
作者：
Fuche, Fabien;Vianney, Anne;Gilbert, Christophe
嗜肺军团菌（Legionella pneumophila）是一种革兰氏阴性病原体，主要存在于水中，以自由生活的形式或在受感染的原生动物体内进行复制。这种细菌也可以通过吸入受污染的气溶胶感染人类，引起一种严重的肺炎，称为军团菌病或军团病。Ⅱ型和Ⅳ型分泌系统参与了L.嗜肺性肺炎现在已经有了很好的记录。尽管生物信息学研究表明I型分泌系统（T1 SS）可能存在于该病原体中，但基于LssB，LssD和TolC蛋白的该系统的功能从未建立。在这里，我们报告的T1 SS的功能，以及它在L的感染周期中的作用的演示。嗜肺菌使用缺失突变体和融合蛋白，我们证明了重复毒素蛋白RtxA是通过LssB-LssD-TolC依赖性机制分泌的。此外，荧光监测和共聚焦显微镜显示，这种T1 SS是进入宿主细胞所必需的，尽管它似乎与细胞内周期无关。总之，这些结果强调了L。pneumophila，通过其T1 SS，在其内化到宿主细胞中。
Legionella pneumophila is a Gram-negative pathogen found mainly in water, either in a free-living form or within infected protozoans, where it replicates. This bacterium can also infect humans by inhalation of contaminated aerosols, causing a severe form of pneumonia called legionellosis or Legionnaires' disease. The involvement of type II and IV secretion systems in the virulence of L. pneumophila is now well documented. Despite bioinformatic studies showing that a type I secretion system (T1SS) could be present in this pathogen, the functionality of this system based on the LssB, LssD, and TolC proteins has never been established. Here, we report the demonstration of the functionality of the T1SS, as well as its role in the infectious cycle of L. pneumophila. Using deletion mutants and fusion proteins, we demonstrated that the repeats-in-toxin protein RtxA is secreted through an LssB-LssD-TolC-dependent mechanism. Moreover, fluorescence monitoring and confocal microscopy showed that this T1SS is required for entry into the host cell, although it seems dispensable to the intracellular cycle. Together, these results underline the active participation of L. pneumophila, via its T1SS, in its internalization into host cells.