Autoregulation of ToxR and Its Regulatory Actions on Major Virulence Gene Loci in Vibrio parahaemolyticus.

Autoregulation of ToxR and Its Regulatory Actions on Major Virulence Gene Loci in Vibrio parahaemolyticus.
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副溶血弧菌ToxR的自身调控及其对主要毒力基因位点的调控作用

DOI:
10.3389/fcimb.2018.00291
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发表时间:
2018
影响因子:
5.7
通讯作者:
Zhou D
Zhou D
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Y;Hu L;Osei-Adjei G;Zhang Y;Yang W;Yin Z;Lu R;Sheng X;Yang R;Huang X;Zhou D

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副溶血性弧菌(Vibrio parahaemolyticus)是引起海产品相关性胃肠炎的主要病原菌,其主要毒力基因位点为T3 SS 1和Vp-PAI(T3 SS 2和tdh 2)。ToxR是弧菌的毒力调节因子。toxR的细胞密度依赖性转录模式及其对T3 SS 1和Vp-PAI的调控作用已有报道,但具体的调控机制尚不清楚。在目前的工作中,我们发现,最高的toxR的转录水平发生在OD 600 = 0.2-0.4,这可能是由于微妙的抑制ToxR和群体感应(QS)主调节AphA。我们还表明,ToxR参与调节小鼠致死性,肠毒性,细胞毒性和溶血活性的副溶血性弧菌。ToxR与T3 SS 1基因座内的多个启动子近端DNA区域结合以抑制它们的转录。此外,ToxR还占据了Vp-PAI基因启动子附近的多个DNA区域,从而激活了它们的转录。因此,ToxR通过直接作用于T3 SS 1和Vp-PAI基因来调控多种毒力表型。这里提供的数据提供了一个更深入的了解ToxR在副溶血性弧菌的监管模式。
Vibrio parahaemolyticus, the leading causative agent of seafood-associated gastroenteritis, harbors two major virulence gene loci T3SS1 and Vp-PAI (T3SS2 and tdh2). ToxR is a virulence regulator of vibrios. Cell density-dependent transcriptional pattern of toxR and its regulatory actions on T3SS1 and Vp-PAI have been previously reported, but the detailed regulatory mechanisms are still obscure. In the present work, we showed that the highest transcription level of toxR occurs at an OD600 = 0.2–0.4, which may be due to the subtle repression of ToxR and the quorum-sensing (QS) master regulator AphA. We also showed that ToxR is involved in regulating the mouse lethality, enterotoxicity, cytotoxicity, and hemolytic activity of V. parahaemolyticus. ToxR binds to the multiple promoter-proximal DNA regions within the T3SS1 locus to repress their transcription. In addition, ToxR occupies the multiple promoter-proximal DNA regions of Vp-PAI locus to activate their transcription. Thus, ToxR regulates the multiple virulence phenotypes via directly acting on the T3SS1 and Vp-PAI genes. Data presented here provide a deeper understanding of the regulatory patterns of ToxR in V. parahaemolyticus.
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