Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors
Shigella chromosomal IpaH proteins are secreted via the type III secretion system and act as effectors
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DOI：
10.1111/j.1365-2958.2006.05547.x
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发表时间：
2007-02-01
影响因子：
3.6
通讯作者：
Sasakawa, Chihiro
中科院分区：
文献类型：
--
作者：
Ashida, Hiroshi;Toyotome, Takahito;Sasakawa, Chihiro
志贺菌具有220 kb的质粒，其主要的毒力决定因子（称为效应子）和III型分泌系统（TTSS）均由质粒专门编码。序列分析表明，S.福氏菌株表明几个ipaH家族基因位于质粒和染色体上，但其染色体IpaH同源物是否可以从志贺菌分泌仍然未知。在这里，我们报告说，S。在福氏杆菌菌株中，YSH 6000编码染色体上的七个ipaH同源基因，并且IpaH蛋白通过TTSS分泌。然而，与IpaB、IpaC和iPad的分泌动力学相比，细菌的IpaH蛋白的分泌动力学表现出延迟。志贺菌进入上皮细胞后，ipaH各基因mRNA的表达量增加，IpaH蛋白由胞内菌分泌。虽然个别染色体ipaH缺失突变体在小鼠肺部感染模型中的发病机制没有明显的变化，但其染色体缺乏所有ipaH基因的Delta ipaH无效突变体减弱至小鼠致死。事实上，对感染Delta ipaH-null的小鼠肺的组织学检查显示出比野生型志贺氏菌诱导的更大的炎症反应，表明染色体IpaH蛋白协同地作为效应子调节宿主炎症反应。
Shigella possess 220 kb plasmid, and the major virulence determinants, called effectors, and the type III secretion system (TTSS) are exclusively encoded by the plasmid. The genome sequences of S. flexneri strains indicate that several ipaH family genes are located on both the plasmid and the chromosome, but whether their chromosomal IpaH cognates can be secreted from Shigella remains unknown. Here we report that S. flexneri strain, YSH6000 encodes seven ipaH cognate genes on the chromosome and that the IpaH proteins are secreted via the TTSS. The secretion kinetics of IpaH proteins by bacteria, however, showed delay compared with those of IpaB, IpaC and IpaD. Expression of the each mRNA of ipaH in Shigella was increased after bacterial entry into epithelial cells, and the IpaH proteins were secreted by intracellular bacteria. Although individual chromosomal ipaH deletion mutants showed no appreciable changes in the pathogenesis in a mouse pulmonary infection model, the Delta ipaH-null mutant, whose chromosome lacks all ipaH genes, was attenuated to mice lethality. Indeed, the histological examination for mouse lungs infected with the Delta ipaH-null showed a greater inflammatory response than induced by wild-type Shigella, suggesting that the chromosomal IpaH proteins act synergistically as effectors to modulate the host inflammatory responses.