title: Sensing the messenger: the diverse ways that bacteria signal through c-di-GMP.
abstract: 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.
authors.affiliation: Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Petya Violinova
authors.initials: PV
authors.lastname: Krasteva
authors.forename: Krista Michelle
authors.initials: KM
authors.lastname: Giglio
authors.forename: Holger
authors.initials: H
authors.lastname: Sondermann
mesh_terms: D001419:Bacteria / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism; D019761:Phosphorus-Oxygen Lyases / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D010727:Phosphoric Diester Hydrolases; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP