AUTHOR=Ren Gai-Xian , Fan Sai , Guo Xiao-Peng , Chen Shiyun , Sun Yi-Cheng 

TITLE=Differential Regulation of c-di-GMP Metabolic Enzymes by Environmental Signals Modulates Biofilm Formation in Yersinia pestis

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00821

DOI=10.3389/fmicb.2016.00821

ISSN=1664-302X

ABSTRACT=<p>Cyclic diguanylate (c-di-GMP) is essential for <italic>Yersinia pestis</italic> biofilm formation, which is important for flea-borne blockage-dependent plague transmission. Two diguanylate cyclases (DGCs), HmsT and HmsD and one phosphodiesterase (PDE), HmsP are responsible for the synthesis and degradation of c-di-GMP in <italic>Y. pestis</italic>. Here, we systematically analyzed the effect of various environmental signals on regulation of the biofilm phenotype, the c-di-GMP levels, and expression of HmsT, HmsD, and HmsP in <italic>Y. pestis</italic>. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl<sub>2</sub>, MgCl<sub>2</sub>, CuSO<sub>4</sub>, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl<sub>2</sub> or NaCl. In addition, we found that HmsD plays a major role in biofilm formation in acidic or redox environments. These environmental signals differentially regulated expression of HmsT, HmsP and HmsD, resulting in changes in the intracellular levels of c-di-GMP in <italic>Y. pestis</italic>. Our results suggest that bacteria can sense various environmental signals, and differentially regulate activity of DGCs and PDEs to coordinately regulate and adapt metabolism of c-di-GMP and biofilm formation to changing environments.</p>