Two-component systems (TCSs) are a prominent sensory system in bacteria. A prototypical TCS comprises a membrane-bound sensor histidine kinase (HK) responsible for sensing the signal and a cytoplasmic response regulator (RR) that controls target gene expression. Signal binding activates a phosphotransfer cascade from the HK to the RR. As a result, the phosphorylated RR undergoes a conformational change that leads to activation of the response. Growing experimental evidence indicates that unphosphorylated RRs may also have regulatory functions, and thus, the classical view that the RR is only active when it is phosphorylated needs to be revisited. In this review, we highlight the most recent findings showing that RRs in the non-phosphorylated state control critical bacterial processes that range from secretion of factors to the host, antibiotic resistance, iron transport, stress response, and cell-wall metabolism to biofilm development.

双组分系统 (TCS) 是细菌中一个突出的感觉系统。原型 TCS 包括负责感知信号的膜结合传感器组氨酸激酶 (HK) 和控制靶基因表达的细胞质反应调节剂 (RR)。信号结合激活从 HK 到 RR 的磷酸转移级联。结果，磷酸化的 RR 发生构象变化，导致反应激活。越来越多的实验证据表明，未磷酸化的 RR 也可能具有调节功能，因此需要重新审视 RR 仅在磷酸化时才具有活性的经典观点。在这篇综述中，我们强调了最近的发现，表明非磷酸化状态的 RR 控制着从因子分泌到宿主的关键细菌过程，