A σE-Mediated Temperature Gauge Controls a Switch from LuxR-Mediated Virulence Gene Expression to Thermal Stress Adaptation in Vibrio alginolyticus.
A σE-Mediated Temperature Gauge Controls a Switch from LuxR-Mediated Virulence Gene Expression to Thermal Stress Adaptation in Vibrio alginolyticus.
复制标题
sigma(E) 介导的温度计控制溶藻弧菌从 LuxR 介导的毒力基因表达到热应激适应的转变
DOI：
10.1371/journal.ppat.1005645
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发表时间：
2016-06
期刊：
影响因子：
6.7
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Gu D;Guo M;Yang M;Zhang Y;Zhou X;Wang Q
在弧菌中，毒力因子的表达通常由LuxR控制，LuxR是主要的群体感应调节因子。在这里，我们调查LuxR和σE，一个替代西格玛因子，在控制毒力相关的基因表达和适应温度升高的人畜共患病病原体溶藻弧菌之间的相互作用。rpoE缺失的溶藻弧菌突变体无法适应各种应激，并且在鱼类中存在生存缺陷。在野生型溶藻弧菌中，LuxR调节的毒力因子的表达随着温度从22°C增加到37°C而增加，但缺乏σE的突变体对温度没有反应，表明σE对于毒力基因的温度依赖性上调至关重要。进一步的分析表明，σE直接结合到luxR启动子中驱动其转录的-10和-35元件。ChIP测定显示，σE在高温下结合luxR、rpoH和rpoE的启动子区（例如，30°C和37°C）。然而，在诱导热应力的较高温度（42°C）下，σE与luxR启动子的结合降低，而其与rpoH和rpoE启动子的结合不变。因此，σE与不同启动子的温度依赖性结合似乎是毒力基因表达和热胁迫适应之间σ E控制的开关的基础。这项研究说明了如何保守的温度反应机制整合到群体感应电路，以调节毒力和压力适应。人畜共患病弧菌的爆发被认为与环境温度的升高密切相关。这种现象背后的机制尚未确定。在这里，我们表明溶藻弧菌外毒素Asp和其他群体感应（QS）调节的毒力因子的表达是由温度升高诱导的，在大约37°C时观察到最大表达。σE通过直接结合luxR启动子的-10和-35区域以驱动其转录，在调节QS主调节因子LuxR以响应温度变化中起重要作用。然而，在较高的热应激温度下，结合到luxR启动子的σE降低，导致luxR转录减少。这种变化是调节σ E控制的毒力基因表达模式的二项式开关机制的基础。此外，我们发现抗σE信号参与了这种胁迫和毒力的相互转换。这项研究表明，一个共同的温度响应机制集成到QS电路，以调节相关弧菌类群的毒力和适应。
In vibrios, the expression of virulence factors is often controlled by LuxR, the master quorum-sensing regulator. Here, we investigate the interplay between LuxR and σE, an alternative sigma factor, during the control of virulence-related gene expression and adaptations to temperature elevations in the zoonotic pathogen Vibrio alginolyticus. An rpoE null V. alginolyticus mutant was unable to adapt to various stresses and was survival-deficient in fish. In wild type V. alginolyticus, the expression of LuxR-regulated virulence factors increased as the temperature was increased from 22°C to 37°C, but mutants lacking σE did not respond to temperature, indicating that σE is critical for the temperature-dependent upregulation of virulence genes. Further analyses revealed that σE binds directly to -10 and -35 elements in the luxR promoter that drive its transcription. ChIP assays showed that σE binds to the promoter regions of luxR, rpoH and rpoE at high temperatures (e.g., 30°C and 37°C). However, at higher temperatures (42°C) that induce thermal stress, σE binding to the luxR promoter decreased, while its binding to the rpoH and rpoE promoters was unchanged. Thus, the temperature-dependent binding of σE to distinct promoters appears to underlie a σE-controlled switch between the expression of virulence genes and adaptation to thermal stress. This study illustrates how a conserved temperature response mechanism integrates into quorum-sensing circuits to regulate both virulence and stress adaptation. Zoonotic Vibrio outbreaks are believed to be closely associated with increases in environmental temperature. The mechanisms underlying this phenomenon have not been defined. Here, we show that the expression of the V. alginolyticus exotoxin Asp and other quorum-sensing (QS)-regulated virulence factors are induced by increasing temperatures, with the maximum expression observed at approximately 37°C. σE plays an essential role in regulating the QS master regulator LuxR in response to temperature shifts by binding directly to the -10 and -35 regions of the luxR promoter to drive its transcription. However, at higher thermal stress temperatures, σE binding to the luxR promoter decreased, resulting in a reduction in luxR transcription. This change underlies a binomial switch mechanism that regulates σE-controlled virulence gene expression patterns. Furthermore, we found that anti-σE signaling was involved in this stress and virulence reciprocal switch. This study suggests that a common temperature response mechanism is integrated into QS circuits to regulate both virulence and adaptation in related Vibrio taxa.