Differential regulation of the hmsCDE operon in Yersinia pestis and Yersinia pseudotuberculosis by the Rcs phosphorelay system

Yersinia pestis, the agent of plague, forms a biofilm in its flea vector to enhance transmission. Yersinia pestis biofilm development is positively regulated by hmsT and hmsD, encoding diguanylate cyclases (DGCs) involved in synthesis of the bacterial second messenger c-di-GMP. rcsA, encoding an auxiliary protein in Rcs phosphorelay, is nonfunctional in Yersinia pestis, while in Yersinia pseudotuberculosis, rcsA is functional and represses biofilms. Previously we showed that Rcs phosphorelay negatively regulates transcription of hmsT in Yersinia pestis and its ancestor Yersinia pseudotuberculosis. In this study, we show that Rcs positively regulates hmsCDE operon (encoding HmsD) in Yersinia pestis; while in the presence of functional rcsA, Rcs represses hmsCDE operon in Yersinia pseudotuberculosis. Loss of rcsA's function in Yersinia pestis not only causes derepression of hmsT but also causes activation of hmsD, which may account for the increased biofilm formation in Yersinia pestis. In addition, differential regulation of the two DGCs, HmsT and HmsD by Rcs may help Yersinia pestis to adapt to different environment.