Sensing the messenger: The diverse ways that bacteria signal through c‐di‐GMP

• Published in: Protein science Vol. 21; no. 7; pp. 929 - 948
• Main Authors: Krasteva, Petya Violinova, Giglio, Krista Michelle, Sondermann, Holger
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2012; Wiley Subscription Services, Inc; Wiley
• Subjects: Bacteria; Bacteria - chemistry; Bacteria - metabolism; Bacterial infections; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; biofilm formation; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; c‐di‐GMP; c‐di‐GMP receptors; diguanylate cyclase; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Life Sciences; Models, Molecular; Pharmaceutical industry; phosphodiesterase; Phosphoric Diester Hydrolases - chemistry; Phosphoric Diester Hydrolases - metabolism; Phosphorus-Oxygen Lyases - chemistry; Phosphorus-Oxygen Lyases - metabolism; Protein Conformation; protein structure; Reviews; Signal Transduction; signaling; Diguanylate cyclase; Biofilm formation; Intracellular signaling; Structural Biology; c-di-GMP signaling; c-di-GMP receptors; Phosphodiesterase
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1002/pro.2093

An intracellular second messenger unique to bacteria, c‐di‐GMP, has gained appreciation as a key player in adaptation and virulence strategies, such as biofilm formation, persistence, and cytotoxicity. Diguanylate cyclases containing GGDEF domains and phosphodiesterases containing either EAL or HD‐GYP domains have been identified as the enzymes controlling intracellular c‐di‐GMP levels, yet little is known regarding signal transmission and the sensory targets for this signaling molecule. Although limited in number, identified c‐di‐GMP receptors in bacteria are characterized by prominent diversity and multilevel impact. In addition, c‐di‐GMP has been shown to have immunomodulatory effects in mammals and several eukaryotic c‐di‐GMP sensors have been proposed. The structural biology of c‐di‐GMP receptors is a rapidly developing field of research, which holds promise for the development of novel therapeutics against bacterial infections. In this review, we highlight recent advances in identifying bacterial and eukaryotic c‐di‐GMP signaling mechanisms and emphasize the need for mechanistic structure–function studies on confirmed signaling targets.