Abstract
Yersinia pestis biofilm formation, controlled by intracellular levels of the second messenger molecule cyclic diguanylate (c-di-GMP), is important for blockage-dependent plague transmission from fleas to mammals. HmsCDE is a tripartite signaling system that modulates intracellular c-di-GMP levels to regulate biofilm formation in Y. pestis. Previously, we found that Y. pestis biofilm formation is stimulated in reducing environments in an hmsCDE-dependent manner. However, the mechanism by which HmsCDE senses the redox state remains elusive. Using a dsbA mutant and the addition of Cu2+ to simulate reducing and oxidizing periplasmic environments, we found that HmsC protein levels are decreased and the HmsC-HmsD protein-protein interaction is weakened in a reducing environment. In addition, we revealed that intraprotein disulphide bonds are critical for HmsC since breakage lowers protein stability and diminishes the interaction with HmsD. Our results suggest that HmsC might play a major role in sensing the environmental changes.
Highlights
Yersinia pestis, the causative agent of plague, is a Gram-negative bacterium that is transmitted to mammals via bites from infected fleas
These results suggest that a reducing periplasmic environment caused by dsbA mutation stimulates biofilm formation in Y. pestis and addition of the oxidant CuSO4 generates an oxidizing periplasmic environment that represses biofilm formation
The super biofilm formation phenotype caused by hmsC mutation could not be complemented by overexpression of dsbA or addition of CuSO4 (Figure 1A, Figure S3), suggesting that HmsC might act as a sensor of the redox environment. These results suggest that the redox periplasmic environment regulates Y. pestis biofilm formation in an hmsCDEdependent manner and HmsC might play an important role in sensing the redox state
Summary
The causative agent of plague, is a Gram-negative bacterium that is transmitted to mammals via bites from infected fleas. Transmission of Y. pestis is greatly enhanced following formation of a bacterial biofilm in the proventriculus of the flea (Eisen et al, 2006, 2007; Eisen and Gage, 2009). Y. pestis biofilms are positively regulated by cyclic-di-GMP (c-di-GMP), a second messenger present in numerous Gram-negative bacteria. The Y. pestis genome encodes two DGCs, HmsT and HmsD. HmsT plays a major role in biofilm formation in vitro, while HmsD plays a more prominent role in blocking proventricular biofilm formation in the flea (Jones et al, 1999; Kirillina et al, 2004; Bobrov et al, 2011; Sun et al, 2011)
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