ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes
ppGpp with DksA controls gene expression in the locus of enterocyte effacement (LEE) pathogenicity island of enterohaemorrhagic Escherichia coli through activation of two virulence regulatory genes
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DOI：
10.1111/j.1365-2958.2006.05217.x
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发表时间：
2006-07-01
影响因子：
3.6
通讯作者：
Tobe, Toru
中科院分区：
文献类型：
--
作者：
Nakanishi, Noriko;Abe, Hiroyuki;Tobe, Toru
一种新的病原体要想出现，它必须获得毒力基因和一个对环境条件变化作出反应的系统。营养素饥饿或生长停滞通过增加ppGpp诱导大肠杆菌中的严格反应。我们发现肠出血性大肠杆菌的粘附能力。大肠杆菌（EHEC）和肠上皮细胞消失（LEE）位点的基因表达通过营养物的下移或进入静止生长期而增强，这两者都增加ppGpp浓度。激活依赖于relA和spoT，其编码用于ppGpp的合成和降解的酶，以及依赖于dksA，其编码严格响应所需的RNA聚合酶辅助蛋白。在诱导RelA表达后，LEE基因转录在20分钟内被激活，即使没有饥饿。两个LEE转录调节因子Ler和Pch的表达被ppGpp激活，并且对于增强LEE基因表达是必需的。此外，ler和pch启动子在体外转录系统中被ppGpp直接激活。这些结果表明，EHEC毒力基因的调控与EHEC的致病基因整合在一起。大肠杆菌的严格反应系统，通过毒力调控基因的调控。
For a new pathogen to emerge, it must acquire both virulence genes and a system for responding to changes in environmental conditions. Starvation of nutrients or growth arrest induces the stringent response in Escherichia coli, via increased ppGpp. We found the adherence capacity of enterohaemorrhagic E. coli (EHEC) and gene expression in the locus of enterocyte effacement (LEE) were enhanced by a downshift in nutrients or by entry into the stationary growth phase, both of which increase the ppGpp concentration. The activation was dependent on relA and spoT, which encode enzymes for the synthesis and degradation of ppGpp, and on dksA, which encodes an RNA polymerase accessory protein required for the stringent response. Upon induction of RelA expression, LEE gene transcription was activated within 20 min, even without starvation. The expression of two LEE transcriptional regulators, Ler and Pch, was activated by ppGpp and essential for the enhancement of LEE gene expression. In addition, the ler and pch promoters were directly activated by ppGpp in an in vitro transcription system. These findings suggest that the regulation of virulence genes in EHEC is integrated with E. coli's stringent response system, through the regulation of virulence regulatory genes.