Cho Kyu Hong, Tryon R Grant, Kim Jeong-Ho
Department of Biology, Indiana State University, Terre Haute, IN, United States.
Department of Biology and Chemistry, Liberty University, Lynchburg, VA, United States.
Front Chem. 2020 Apr 21;8:264. doi: 10.3389/fchem.2020.00264. eCollection 2020.
The majority of bacteria in the natural environment organize themselves into communal biofilms. Biofilm formation benefits bacteria conferring resistance to harmful molecules (e.g., antibiotics, disinfectants, and host immune factors) and coordinating their gene expression through quorum sensing (QS). A primary signaling molecule promoting bacterial biofilm formation is the universal second messenger cyclic di-GMP. This dinucleotide predominantly controls the gene expression of motility, adhesins, and capsule production to coordinate biofilm formation. Cyclic di-GMP is synthesized by diguanylate cyclases (DGCs) that have a GGDEF domain and is degraded by phosphodiesterases (PDEs) containing either an EAL or an HD-GYP domain. Since high cellular c-di-GMP concentrations are correlated with promoting the ability of bacteria to form biofilms, numerous research endeavors to identify chemicals capable of inhibiting the c-di-GMP synthesis activity of DGCs have been performed in order to inhibit bacterial biofilm formation. This review describes currently identified chemical inhibitors that disturb the activity of DGCs and the methods of screening and assay for their discovery.
自然环境中的大多数细菌会自行组织形成群落生物膜。生物膜的形成对细菌有益，使其能够抵抗有害分子（如抗生素、消毒剂和宿主免疫因子），并通过群体感应（QS）协调其基因表达。促进细菌生物膜形成的一种主要信号分子是通用的第二信使环二鸟苷酸（cyclic di-GMP）。这种二核苷酸主要控制运动性、粘附素和荚膜产生的基因表达，以协调生物膜的形成。环二鸟苷酸由具有GGDEF结构域的二鸟苷酸环化酶（DGCs）合成，并由含有EAL或HD-GYP结构域的磷酸二酯酶（PDEs）降解。由于细胞内环二鸟苷酸的高浓度与促进细菌形成生物膜的能力相关，为了抑制细菌生物膜的形成，人们进行了大量研究，试图鉴定能够抑制二鸟苷酸环化酶环二鸟苷酸合成活性的化学物质。这篇综述描述了目前已鉴定出的干扰二鸟苷酸环化酶活性的化学抑制剂，以及发现这些抑制剂的筛选和检测方法。
