National Key Laboratory of Agricultural Microbiology and Hubei Hongshan Laboratory, College of Life Science and Technology, Huazhong Agricultural University, 1 Shizishan Street, Wuhan, Hubei 430070, PR China.
Institute of Agro-Product Processing, Jiangsu Academy of Agricultural Sciences, 50 Zhongling Street, Nanjing, Jiangsu 210014, PR China.
FEMS Microbiol Rev. 2023 Jul 5;47(4). doi: 10.1093/femsre/fuad034.
The widespread bacterial second messenger c-di-GMP is responsible for regulating many important physiological functions such as biofilm formation, motility, cell differentiation, and virulence. The synthesis and degradation of c-di-GMP in bacterial cells depend, respectively, on diguanylate cyclases and c-di-GMP-specific phosphodiesterases. Since c-di-GMP metabolic enzymes (CMEs) are often fused to sensory domains, their activities are likely controlled by environmental signals, thereby altering cellular c-di-GMP levels and regulating bacterial adaptive behaviors. Previous studies on c-di-GMP-mediated regulation mainly focused on downstream signaling pathways, including the identification of CMEs, cellular c-di-GMP receptors, and c-di-GMP-regulated processes. The mechanisms of CME regulation by upstream signaling modules received less attention, resulting in a limited understanding of the c-di-GMP regulatory networks. We review here the diversity of sensory domains related to bacterial CME regulation. We specifically discuss those domains that are capable of sensing gaseous or light signals and the mechanisms they use for regulating cellular c-di-GMP levels. It is hoped that this review would help refine the complete c-di-GMP regulatory networks and improve our understanding of bacterial behaviors in changing environments. In practical terms, this may eventually provide a way to control c-di-GMP-mediated bacterial biofilm formation and pathogenesis in general.
广泛存在的细菌第二信使环二鸟苷酸（c-di-GMP）负责调节许多重要的生理功能，如生物膜形成、运动性、细胞分化和毒力。细菌细胞中 c-di-GMP 的合成和降解分别依赖于双鸟苷酸环化酶和 c-di-GMP 特异性磷酸二酯酶。由于 c-di-GMP 代谢酶（CMEs）通常与感应结构域融合，它们的活性可能受到环境信号的控制，从而改变细胞内 c-di-GMP 水平并调节细菌的适应性行为。以前关于 c-di-GMP 介导的调节的研究主要集中在下游信号通路，包括 CMEs、细胞 c-di-GMP 受体和 c-di-GMP 调节的过程的鉴定。上游信号模块对 CME 调节的机制受到较少关注，导致对 c-di-GMP 调节网络的理解有限。我们在这里回顾了与细菌 CME 调节相关的感觉域的多样性。我们特别讨论了那些能够感知气态或光信号的结构域以及它们用于调节细胞内 c-di-GMP 水平的机制。希望本综述能够帮助完善完整的 c-di-GMP 调节网络，并加深我们对细菌在不断变化的环境中的行为的理解。实际上，这可能最终为控制 c-di-GMP 介导的细菌生物膜形成和普遍的发病机制提供一种方法。
