Ren Gai-Xian, Fan Sai, Guo Xiao-Peng, Chen Shiyun, Sun Yi-Cheng
MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
Institute of Nutrition and Food Hygiene, Beijing Centre for Disease Control and Prevention Beijing, China.
Front Microbiol. 2016 Jun 3;7:821. doi: 10.3389/fmicb.2016.00821. eCollection 2016.
Cyclic diguanylate (c-di-GMP) is essential for Yersinia pestis 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 Y. pestis. 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 Y. pestis. Biofilm formation was higher in the presence of non-lethal high concentration of CaCl2, MgCl2, CuSO4, sucrose, sodium dodecyl sulfate, or dithiothreitol, and was lower in the presence of FeCl2 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 Y. pestis. 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.
环二鸟苷酸（c-di-GMP）对于鼠疫耶尔森菌生物膜的形成至关重要，而生物膜的形成对于跳蚤传播的依赖堵塞的鼠疫传播具有重要意义。两种鸟苷酸环化酶（DGCs），即HmsT和HmsD以及一种磷酸二酯酶（PDE），即HmsP负责鼠疫耶尔森菌中c-di-GMP的合成和降解。在此，我们系统地分析了各种环境信号对鼠疫耶尔森菌生物膜表型、c-di-GMP水平以及HmsT、HmsD和HmsP表达的调控作用。在存在非致死性高浓度的氯化钙、氯化镁、硫酸铜、蔗糖、十二烷基硫酸钠或二硫苏糖醇的情况下，生物膜形成较高，而在存在氯化亚铁或氯化钠的情况下则较低。此外，我们发现HmsD在酸性或氧化还原环境中的生物膜形成中起主要作用。这些环境信号差异调节HmsT、HmsP和HmsD的表达，导致鼠疫耶尔森菌细胞内c-di-GMP水平发生变化。我们的结果表明，细菌能够感知各种环境信号，并差异调节DGCs和PDEs的活性，以协调调节和适应c-di-GMP的代谢以及生物膜形成以应对不断变化的环境。
