Signaling between two interacting sensor kinases promotes biofilms and colonization by a bacterial symbiont

Summary Cells acclimate to fluctuating environments by utilizing sensory circuits. One common sensory pathway used by bacteria is two‐component signaling ( TCS ), composed of an environmental sensor [the sensor kinase ( SK )] and a cognate, intracellular effector [the response regulator ( RR )]. The squid symbiont V ibrio fischeri uses an elaborate TCS phosphorelay containing a hybrid SK , RscS , and two RR s, SypE and SypG , to control biofilm formation and host colonization. Here, we found that another hybrid SK , SypF , was essential for biofilms by functioning downstream of RscS to directly control SypE and SypG . Surprisingly, although wild‐type SypF functioned as an SK   in vitro , this activity was dispensable for colonization. In fact, only a single non‐enzymatic domain within SypF , the HPt domain, was critical in vivo . Remarkably, this domain within SypF interacted with RscS to permit a bypass of RscS ‘s own HPt domain and SypF ‘s enzymatic function. This represents the first in vivo example of a functional SK that exploits the enzymatic activity of another SK , an adaptation that demonstrates the elegant plasticity in the arrangement of TCS regulators.