RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus
RtxA1-Induced Expression of the Small GTPase Rac2 Plays a Key Role in the Pathogenicity of Vibrio vulnificus
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DOI：
10.1086/648612
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发表时间：
2010-01-01
影响因子：
6.4
通讯作者：
Lee, Tae-Hoon
中科院分区：
文献类型：
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作者：
Chung, Kyoung-Jin;Cho, Eun-Jin;Lee, Tae-Hoon
感染人类病原体创伤弧菌导致宿主细胞中通过NAD（P）H氧化酶（Nox）产生活性氧（ROS）。在本研究中，我们采用突变体创伤弧菌菌株，以确定一个重要的毒力因子负责这种ROS的产生。我们发现创伤弧菌表达的毒素A1重复序列（RtxA1）通过Nox 1诱导肠上皮细胞产生大量ROS，最终导致细胞死亡。此外，RtxA1调节小的GT3 Rac 2，已知其在Nox的激活中起重要作用。当小鼠通过口服方法感染时，与野生型细菌相比，RtxA1缺陷型创伤弧菌突变体无法诱导肠道内的ROS产生，并且未能导致死亡。这些发现有力地表明，RTxA1诱导的Rac2表达是创伤弧菌致病性的关键步骤。
Infection with the human pathogen Vibrio vulnificus leads to the generation of reactive oxygen species (ROS) via NAD(P) H oxidase (Nox) in host cells. In the present study, we employed mutant V. vulnificus strains to identify an essential virulence factor responsible for this ROS generation. We found that repeats-in-toxin A1 (RtxA1) expressed by V. vulnificus acts via Nox1 to induce significant ROS generation in the intestine epithelial cells, which ultimately results in cell death. Furthermore, RtxA1 modulates the small GTPase Rac2, which is known to play an important role in the activation of Nox. When mice were infected by the oral method, in contrast with the wild-type bacteria, an RtxA1-deficient V. vulnificus mutant was unable to induce ROS generation within the intestine and failed to cause death. These findings strongly suggest that RtxA1-induced Rac2 expression is a critical step underlying the pathogenicity of V. vulnificus.