Acosta Nicole, Pukatzki Stefan, Raivio Tracy L
Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada.
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Infect Immun. 2015 Jun;83(6):2396-408. doi: 10.1128/IAI.03056-14. Epub 2015 Mar 30.
Bacteria possess signal transduction pathways capable of sensing and responding to a wide variety of signals. The Cpx envelope stress response, composed of the sensor histidine kinase CpxA and the response regulator CpxR, senses and mediates adaptation to insults to the bacterial envelope. The Cpx response has been implicated in the regulation of a number of envelope-localized virulence determinants across bacterial species. Here, we show that activation of the Cpx pathway in Vibrio cholerae El Tor strain C6706 leads to a decrease in expression of the major virulence factors in this organism, cholera toxin (CT) and the toxin-coregulated pilus (TCP). Our results indicate that this occurs through the repression of production of the ToxT regulator and an additional upstream transcription factor, TcpP. The effect of the Cpx response on CT and TCP expression is mostly abrogated in a cyclic AMP receptor protein (CRP) mutant, although expression of the crp gene is unaltered. Since TcpP production is controlled by CRP, our data suggest a model whereby the Cpx response affects CRP function, which leads to diminished TcpP, ToxT, CT, and TCP production.
细菌拥有能够感知并响应多种信号的信号转导通路。由传感器组氨酸激酶CpxA和响应调节因子CpxR组成的Cpx包膜应激反应，可感知并介导细菌对包膜损伤的适应性反应。Cpx反应与多种细菌物种中一些包膜定位的毒力决定因素的调控有关。在此，我们表明，霍乱弧菌El Tor菌株C6706中Cpx通路的激活导致该生物体中主要毒力因子霍乱毒素（CT）和毒素共调节菌毛（TCP）的表达降低。我们的结果表明，这是通过抑制ToxT调节因子和另一种上游转录因子TcpP的产生而发生的。尽管crp基因的表达未改变，但在环磷酸腺苷受体蛋白（CRP）突变体中，Cpx反应对CT和TCP表达的影响大多被消除。由于TcpP的产生受CRP控制，我们的数据提出了一个模型，即Cpx反应影响CRP功能，从而导致TcpP、ToxT、CT和TCP的产生减少。
