Glucose-Binding of Periplasmic Protein GltB Activates GtrS-GltR Two-Component System in .

A two-component system GtrS-GltR is required for glucose transport activity in and plays a key role during -host interactions. However, the mechanism of action of GtrS-GltR has not been definitively established. Here, we show that , which encodes a periplasmic glucose binding protein, is essential for the glucose-induced activation of GtrS-GltR in . We determined that GltB is capable of binding to membrane regulatory proteins including GtrS, the sensor kinase of the GtrS-GltR TCS. We observed that alanine substitution of glucose-binding residues abolishes the ability of GltB to promote the activation of GtrS-GltR. Importantly, like the deletion mutant, deletion mutant showed attenuated virulence in both and mouse models of infection. In addition, using CHIP-seq experiments, we showed that the promoter of is the major in vivo target of GltR. Collectively, these data suggest that periplasmic binding protein GltB and GtrS-GltR TCS form a complex regulatory circuit that regulates the virulence of in response to glucose.