Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, United States of America.
Yale Microbial Sciences Institute, West Haven, Connecticut, United States of America.
PLoS Genet. 2020 May 11;16(5):e1008722. doi: 10.1371/journal.pgen.1008722. eCollection 2020 May.
To survive an environmental stress, organisms must detect the stress and mount an appropriate response. One way that bacteria do so is by phosphorelay systems that respond to a stress by activating a regulator that modifies gene expression. To ensure an appropriate response, a given regulator is typically activated solely by its cognate phosphorelay protein(s). However, we now report that the regulator RcsB is activated by both cognate and non-cognate phosphorelay proteins, depending on the condition experienced by the bacterium Salmonella enterica serovar Typhimurium. The RcsC and RcsD proteins form a phosphorelay that activates their cognate regulator RcsB in response to outer membrane stress and cell wall perturbations, conditions Salmonella experiences during infection. Surprisingly, the non-cognate phosphorelay protein BarA activates RcsB during logarithmic growth in Luria-Bertani medium in three ways. That is, BarA's cognate regulator SirA promotes transcription of the rcsDB operon; the SirA-dependent regulatory RNAs CsrB and CsrC further increase RcsB-activated gene transcription; and BarA activates RcsB independently of the RcsC, RcsD, and SirA proteins. Activation of a regulator by multiple sensors broadens the spectrum of environments in which a set of genes is expressed without evolving binding sites for different regulators at each of these genes.
为了在环境压力下生存，生物体必须检测到压力并做出适当的反应。细菌通过磷酸接力系统来实现这一点，该系统通过激活调节因子来响应压力，从而改变基因表达。为了确保适当的反应，给定的调节剂通常仅被其同源磷酸接力蛋白激活。然而，我们现在报告说，调节因子 RcsB 可被同源和非同源磷酸接力蛋白激活，具体取决于沙门氏菌属鼠伤寒血清型细菌所经历的情况。RcsC 和 RcsD 蛋白形成磷酸接力系统，在感受到外膜压力和细胞壁扰动时，激活其同源调节因子 RcsB，这些都是沙门氏菌在感染过程中经历的情况。令人惊讶的是，非同源磷酸接力蛋白 BarA 在 Luria-Bertani 培养基中对数生长期以三种方式激活 RcsB。也就是说，BarA 的同源调节因子 SirA 促进 rcsDB 操纵子的转录；依赖 SirA 的调节 RNA CsrB 和 CsrC 进一步增加 RcsB 激活的基因转录；BarA 独立于 RcsC、RcsD 和 SirA 蛋白激活 RcsB。多个传感器激活一个调节剂可以扩大一组基因表达的环境范围，而无需在这些基因的每个基因上进化出针对不同调节剂的结合位点。
