Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Microbiology (Reading). 2011 Jun;157(Pt 6):1620-1628. doi: 10.1099/mic.0.046235-0. Epub 2011 Mar 10.
The human pathogen Vibrio cholerae uses quorum sensing to regulate the expression of a number of phenotypes, including virulence factor production, in response to changes in cell density. It produces small molecules called autoinducers that increase in concentration as cell density increases, and these autoinducers bind to membrane sensors once they reach a certain threshold. This binding leads to signalling through a downstream phosphorelay pathway to alter the expression of the transcriptional regulator HapR. Previously, it was shown that the VarS/VarA two-component system acts on a component of the phosphorelay pathway upstream of HapR to regulate HapR expression levels. Here, we show that in addition to this mechanism of regulation, VarS and VarA also indirectly modulate HapR protein activity. This modulation is mediated by the small RNA CsrB but is independent of the known quorum-sensing system that links the autoinducers to HapR. Thus, the VarS/VarA two-component system intersects with the quorum-sensing network at two levels. In both cases, the effect of VarS and VarA on quorum sensing is dependent on the Csr small RNAs, which regulate carbon metabolism, suggesting that V. cholerae may integrate nutrient status and cell density sensory inputs to tailor its gene expression profile more precisely to surrounding conditions.
人类病原体霍乱弧菌利用群体感应来调节许多表型的表达，包括毒力因子的产生，以响应细胞密度的变化。它产生称为自动诱导物的小分子，随着细胞密度的增加而增加浓度，并且这些自动诱导物一旦达到一定阈值就会与膜传感器结合。这种结合通过下游磷酸传递途径进行信号传递，从而改变转录调节因子 HapR 的表达。以前已经表明，VarS/VarA 双组分系统作用于 HapR 上游磷酸传递途径的一个组分，以调节 HapR 的表达水平。在这里，我们表明，除了这种调节机制外，VarS 和 VarA 还间接调节 HapR 蛋白活性。这种调节是由小 RNA CsrB 介导的，但不依赖于将自动诱导物与 HapR 联系起来的已知群体感应系统。因此，VarS/VarA 双组分系统在两个水平上与群体感应网络交叉。在这两种情况下，VarS 和 VarA 对群体感应的影响都依赖于 Csr 小 RNA，它调节碳代谢，这表明霍乱弧菌可能整合营养状态和细胞密度感应输入，以更精确地调整其基因表达谱以适应周围环境。
