Role of Heat Shock Proteases in Quorum-Sensing-Mediated Regulation of Biofilm Formation by Vibrio Species.
Role of Heat Shock Proteases in Quorum-Sensing-Mediated Regulation of Biofilm Formation by Vibrio Species.
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DOI：
10.1128/mbio.02086-17
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发表时间：
2018-01-02
期刊：
影响因子：
6.4
通讯作者：
Lee KH
中科院分区：
文献类型：
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作者：
Lee KJ;Jung YC;Park SJ;Lee KH
荚膜多糖（CPS）是创伤弧菌（Vibriovulnificus）生物膜的重要组成部分。当生物膜成熟时，由群体感应（QS）主调节因子SmcR诱导CPS产生。然而，创伤弧菌生物膜形成的热休克条件下没有表现出分散阶段。CPS基因簇的转录物在热暴露的细胞中处于基础水平，这是由于SmcR的细胞水平降低。至少有两种蛋白酶诱导的热休克，ClpPA和Lon，负责确定SmcR的不稳定性。在体外和体内试验表明，SmcR水平的调节，通过这些蛋白酶的蛋白水解，优先单体SmcR的蛋白水解。因此，当细菌被热处理时，QS不诱导CPS产生。对其他弧菌属物种进行的进一步研究表明，高温通过增加其QS主调节因子的蛋白水解使QS回路失活，从而导致QS调节表型的改变，包括生物膜形成。术语“群体感应机制”用于描述多种细菌细胞密度依赖性活性，其通过感应信号传导分子和随后的信号转导至主调节因子来实现。这些众所周知的细菌调节系统调节病原菌中多种毒力因子的表达和生物膜的构建。已经有许多研究设计通过使用小分子拮抗群体感应调节组分或干扰信号分子来控制细菌群体感应。在本研究中，我们发现致病性弧菌物种的群体感应调节电路被灭活热休克处理通过高度增加的主转录因子的蛋白水解。我们的研究结果显示了一种新的群体失活模式，即使周围的信号分子可能达到代表高细胞密度的水平，也可以在高但非致死温度的条件下实现。
Capsular polysaccharide (CPS) is essential for the dispersal of biofilms formed by the pathogenic bacterium Vibrio vulnificus. CPS production is induced by the quorum-sensing (QS) master regulator SmcR when biofilms mature. However, V. vulnificus biofilms formed under heat shock conditions did not exhibit the dispersion stage. Transcripts of the CPS gene cluster were at basal levels in the heat-exposed cell owing to reduced cellular levels of SmcR. At least two proteases induced by heat shock, ClpPA and Lon, were responsible for determining the instability of SmcR. In vitro and in vivo assays demonstrated that SmcR levels were regulated via proteolysis by these proteases, with preferential proteolysis of monomeric SmcR. Thus, CPS production was not induced by QS when bacteria were heat treated. Further studies performed with other Vibrio species demonstrated that high temperature deactivated the QS circuits by increased proteolysis of their QS master regulators, thus resulting in alterations to the QS-regulated phenotypes, including biofilm formation. The term "quorum-sensing mechanism" is used to describe diverse bacterial cell density-dependent activities that are achieved by sensing of the signaling molecules and subsequent signal transduction to the master regulators. These well-known bacterial regulatory systems regulate the expression of diverse virulence factors and the construction of biofilms in pathogenic bacteria. There have been numerous studies designed to control bacterial quorum sensing by using small molecules to antagonize the quorum-sensing regulatory components or to interfere with the signaling molecules. In the present study, we showed that the quorum-sensing regulatory circuits of pathogenic Vibrio species were deactivated by heat shock treatment via highly increased proteolysis of the master transcription factors. Our results showed a new mode of quorum deactivation which can be achieved under conditions of high but nonlethal temperature even if the ambient signaling molecules may reach the levels representing high cell density.