HmsC, a periplasmic protein, controls biofilm formation via repression of HmsD, a diguanylate cyclase in Yersinia pestis.

Yersinia pestis, the cause of plague, forms a biofilm in the foregut of its flea vector to enhance transmission. Biofilm formation in Y. pestis is controlled by the intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP). HmsT and Y3730, the two diguanylate cyclases (DGC) in Y. pestis, are responsible for the synthesis of c-di-GMP. Y3730, which we name here as HmsD, has little effect on in vitro biofilms, but has a major effect on biofilm formation in the flea. The mechanism by which HmsD plays differential roles in vivo and in vitro is not understood. In this study, we show that hmsD is part of a three-gene operon (y3729-31), which we designate as hmsCDE. Deletion of hmsC resulted in increased, hmsD-dependent biofilm formation, while deletion or overexpression of hmsE did not affect biofilm formation. Localization experiments suggest that HmsC resides in the periplasmic space. In addition, we provide evidence that HmsC might interact directly with the periplasmic domain of HmsD and cause the proteolysis of HmsD. We propose that HmsC senses the environmental signals, which in turn regulates HmsD, and controls the c-di-GMP synthesis and biofilm formation in Y. pestis.

Ren GX ，Yan HQ ，Zhu H ，Guo XP ，Sun YC ... -  《-》

CsrA-Mediated Translational Activation of the hmsE mRNA Enhances HmsD-Dependent C-di-GMP-Enabled Biofilm Production in Yersinia pestis.

Silva-Rohwer AR ，Held K ，Yakhnin H ，Babitzke P ，Vadyvaloo V ... -  《-》

HmsC Controls Yersinia pestis Biofilm Formation in Response to Redox Environment.

Ren GX ，Guo XP ，Sun YC 《Frontiers in Cellular and Infection Microbiology》

The Yersinia pestis HmsCDE regulatory system is essential for blockage of the oriental rat flea (Xenopsylla cheopis), a classic plague vector.

The second messenger molecule cyclic diguanylate is essential for Yersinia pestis biofilm formation that is important for blockage-dependent plague transmission from fleas to mammals. Two diguanylate cyclases (DGCs) HmsT and Y3730 (HmsD) are responsible for biofilm formation in vitro and biofilm-dependent blockage in the oriental rat flea Xenopsylla cheopis respectively. Here, we have identified a tripartite signalling system encoded by the y3729-y3731 operon that is responsible for regulation of biofilm formation in different environments. We present genetic evidence that a putative inner membrane-anchored protein with a large periplasmic domain Y3729 (HmsC) inhibits HmsD DGC activity in vitro while an outer membrane Pal-like putative lipoprotein Y3731 (HmsE) counteracts HmsC to activate HmsD in the gut of X. cheopis. We propose that HmsE is a critical element in the transduction of environmental signal(s) required for HmsD-dependent biofilm formation.

Bobrov AG ，Kirillina O ，Vadyvaloo V ，Koestler BJ ，Hinz AK ，Mack D ，Waters CM ，Perry RD ... -  《-》

Differential control of Yersinia pestis biofilm formation in vitro and in the flea vector by two c-di-GMP diguanylate cyclases.

Sun YC ，Koumoutsi A ，Jarrett C ，Lawrence K ，Gherardini FC ，Darby C ，Hinnebusch BJ ... -  《PLoS One》