Institut für Biologie-Mikrobiologie, Freie Universität Berlin, Berlin, Germany.
J Biotechnol. 2012 Jul 31;160(1-2):10-6. doi: 10.1016/j.jbiotec.2011.12.024. Epub 2011 Dec 31.
Most bacteria can exist in either a planktonic-motile single-cell state or an adhesive multicellular state known as a biofilm. Biofilms cause medical problems and technical damage since they are resistant against antibiotics, disinfectants or the attacks of the immune system. In recent years it has become clear that most bacteria use cyclic diguanylate (c-di-GMP) as a biofilm-promoting second messenger molecule. C-di-GMP is produced by GGDEF-domain-containing diguanylate cyclases and is degraded by phosphodiesterases featuring EAL or HD-GYP domains. Many bacterial species possess multiple proteins with GGDEF and EAL domains, which actually belong to the most abundant protein families in genomic data bases. Via an unprecedented variety of effector components, which include c-di-GMP-binding proteins as well as RNAs, c-di-GMP controls a wide range of targets that down-regulate motility, stimulate adhesin and biofilm matrix formation or even control virulence gene expression. Moreover, local c-di-GMP signaling in macromolecular complexes seems to allow the independent and parallel control of different output reactions. In this review, we use Escherichia coli as a paradigm for c-di-GMP signaling. Despite the huge diversity of components and molecular processes involved in biofilm formation throughout the bacterial kingdom, c-di-GMP signaling represents a unifying principle, which suggests that the enzymes that make and break c-di-GMP may be promising targets for anti-biofilm drugs.
大多数细菌可以存在于浮游生物-运动的单细胞状态或称为生物膜的粘附多细胞状态。生物膜会导致医疗问题和技术损坏，因为它们对抗生素、消毒剂或免疫系统的攻击具有抵抗力。近年来，人们已经清楚地认识到，大多数细菌使用环二鸟苷酸（c-di-GMP）作为促进生物膜形成的第二信使分子。c-di-GMP 由含有 GGDEF 结构域的二鸟苷酸环化酶产生，并被具有 EAL 或 HD-GYP 结构域的磷酸二酯酶降解。许多细菌物种拥有多个具有 GGDEF 和 EAL 结构域的蛋白质，这些蛋白质实际上属于基因组数据库中最丰富的蛋白质家族。通过前所未有的多种效应子成分，包括 c-di-GMP 结合蛋白和 RNA，c-di-GMP 控制着广泛的靶标，这些靶标下调运动性、刺激粘附素和生物膜基质形成，甚至控制毒力基因表达。此外，大分子复合物中的局部 c-di-GMP 信号似乎允许对不同输出反应进行独立和平行的控制。在这篇综述中，我们以大肠杆菌作为 c-di-GMP 信号的范例。尽管在整个细菌王国中，生物膜形成涉及到巨大的成分和分子过程多样性，但 c-di-GMP 信号代表了一个统一的原则，这表明产生和分解 c-di-GMP 的酶可能是抗生物膜药物的有希望的靶标。
