VBNC（活的非可培养状态）是细菌在不利环境条件下的一种生存策略。病原菌的VBNC状态对流行病学监测、环境安全和公共健康构成重要的潜在风险。迄今为止，细菌VBNC的形成与复苏机制尚未被揭示。RIP（蛋白质受控膜内水解）信号转导通路触发的调控子ToxR水解可能参与VBNC的形成过程。环境胁迫应答反应可激活TA（毒素-抗毒素）系统活性，通过降解mRNA和抑制DNA复制等来调节细胞的生长与休眠。作为海水养殖病害中的重要人畜共患病原，溶藻弧菌遇到环境胁迫时可以VBNC形式分布于自然水生环境中。本课题以该病原为研究对象，拟研究在不同环境胁迫下由RIP信号通路介导的ToxR蛋白水解并进入VBNC状态的调控规律，同时探究这一环境胁迫应答与TA系统的级联关系及调控机制，从而初步阐明溶藻弧菌以ToxR为分子开关的VBNC形成机制和调控网络框架。

The viable but nonculturable (VBNC) cells have been accepted as a survival strategy of bacteria exposed to adverse environmental circumstances. Diseases caused by foodborne or waterborne pathogens in the VBNC state are emerging. The VBNC pathogens have the ability to evade conventional microbiological detection methods. Moreover, pathogenic bacteria in the VBNC state can regain virulence after resuscitation into culturable cells under suitable conditions. All these pose a significant and potential environmental and public health risk. So far, not much is in fact known about the molecular mechanisms underlying VBNC state induction and resuscitation. The loss of regulator ToxR, by regulated intramembrane proteolysis (RIP), may be associated with entry of Vibrio into the VBNC state. Toxin-antitoxin (TA) systems were found to be important in regulation of cell growth and dormancy, which is realized by inhibition of translation and protein biosynthesis caused by free toxin. The ppGpp synthesized in response to the environmental stress can controls the activity of TA modules. As an important zoonotic pathogen in marine aquaculture industries, Vibrio alginolyticus can enter into the VBNC state when exposed to conditions adverse to growth in the natural aquatic environment. In order to illuminate the mechanisms and basic regulatory network of VBNC state switched by ToxR, we set to explore cognation and regulating characteristics between the proteolysis of ToxR by RIP and the entry of V. alginolyticus into the VBNC state. Also, the genetic pathways in response to stresses, which undergo RIP signal cascade associated with TA system, will be delve deeply. All these expected results will reveal and illuminate preliminary the molecular mechanism in VBNC state formation, which will helpful to go into more detail on the comprehensive knowledge of the VBNC state induction in V. alginolyticus and other pathogenic bacteria.