The flagellar sigma factor FliA regulates adhesion and invasion of Crohn disease-associated Escherichia coli via a cyclic dimeric GMP-dependent pathway
The flagellar sigma factor FliA regulates adhesion and invasion of Crohn disease-associated Escherichia coli via a cyclic dimeric GMP-dependent pathway
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DOI：
10.1074/jbc.m702800200
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发表时间：
2007-11-16
影响因子：
4.8
通讯作者：
Darfeuille-Michaud, Arlette
中科院分区：
文献类型：
--
作者：
Claret, Laurent;Miquel, Sylvie;Darfeuille-Michaud, Arlette
克罗恩病相关的黏附侵袭性大肠杆菌（AIEC）菌株LF82对肠上皮细胞的侵袭依赖于表面附属物，如1型菌毛和鞭毛。AIEC菌株LF82中鞭毛的缺失会导致1型菌毛随之缺失。在此，我们表明鞭毛调节因子、转录激活因子FlhD₂C₂以及σ因子FliA参与鞭毛和1型菌毛合成的协调。在缺失这些调节因子的缺失突变体中，1型菌毛合成、黏附和侵袭能力严重下降。反式单独表达的FliA足以恢复LF82 - ΔflhD和LF82 - ΔfliA突变体中的这些缺陷。我们将1型菌毛的缺失与LF82 - ΔfliA突变体中依赖FliA的yhjH基因表达降低相关联。YhjH是一种EAL结构域磷酸二酯酶，参与细菌第二信使环二鸟苷酸（c - di - GMP）的降解。yhjH或另一种c - di - GMP磷酸二酯酶yahA的表达增加，可部分恢复LF82 - ΔfliA突变体中1型菌毛合成、黏附和侵袭能力。在LF82 - ΔfliA突变体中，参与c - di - GMP合成的GGDEF结构域双鸟苷酸环化酶基因yaiC的缺失也可部分恢复这些缺陷，而c - di - GMP受体YcgR的过表达则具有相反的效果。这些发现表明，在AIEC菌株LF82中，FliA是连接鞭毛和1型菌毛合成的关键调节成分，并且它对1型菌毛的作用至少部分是通过c - di - GMP依赖途径介导的。
The invasion of intestinal epithelial cells by the Crohn disease-associated adherent-invasive Escherichia coli (AIEC) strain LF82 depends on surface appendages, such as type 1 pili and flagella. The absence of flagella in the AIEC strain LF82 results in a concomitant loss of type 1 pili. Here, we show that flagellar regulators, transcriptional activator FlhD(2)C(2), and sigma factor FliA are involved in the coordination of flagellar and type 1 pili synthesis. In the deletion mutants lacking these regulators, type 1 pili synthesis, adhesion, and invasion were severely decreased. FliA expressed alone in trans was sufficient to restore these defects in both the LF82-Delta flhD and LF82-Delta fliA mutants. We related the loss of type 1 pili to the decreased expression of the FliA-dependent yhjH gene in the LF82-Delta fliA mutant. YhjH is an EAL domain phosphodiesterase involved in degradation of the bacterial second messenger cyclic dimeric GMP (c-di-GMP). Increased expression of either yhjH or an alternative c-di-GMP phosphodiesterase, yahA, partially restored type 1 pili synthesis, adhesion, and invasion in the LF82-Delta fliA mutant. Deletion of the GGDEF domain diguanylate cyclase gene, yaiC, involved in c-di-GMP synthesis in the LF82-Delta fliA mutant also partially restored these defects, whereas overexpression of the c-di-GMP receptor YcgR had the opposite effect. These findings show that in the AIEC strain LF82, FliA is a key regulatory component linking flagellar and type 1 pili synthesis and that its effect on type 1 pili is mediated, at least in part, via a c-di-GMP-dependent pathway.