Cyclic di-GMP Signalling and Regulation in Bacteria
J. Maxwell Dow, Yvonne McCarthy, Karen O'Donovan, Delphine Caly and Robert P. Ryan
from: Bacterial Regulatory Networks (Edited by: Alain A.M. Filloux). Caister Academic Press, U.K. (2012)
Cyclic di-GMP is now recognised as an almost universal second messenger in eubacteria that acts to regulate a wide range of functions including developmental transitions, adhesion, biofilm formation, motility and the synthesis of virulence factors. Cyclic di-GMP is synthesised from two GTP molecules by diguanylate cyclases that have a GGDEF domain and degraded by phosphodiesterases with either an EAL or HD-GYP domain. These proteins often have associated signal input domains, suggesting that their enzymatic activity may be modulated by different environmental or cellular cues. Cyclic di-GMP exerts a regulatory action through binding to diverse receptors that include a small protein domain called PilZ, transcription factors, enzymatically-inactive GGDEF, EAL or HD-GYP domains and riboswitches. The multiplicity of GGDEF, EAL and HD-GYP proteins together with a range of receptors within the same bacterial cell indicates the considerable complexity of cyclic di-GMP signalling. This has led to the concept of discrete pools of the nucleotide that are generated locally and act to influence intimately associated targets. A number of signalling proteins may be organised in a regulatory network to control a common function(s). Understanding cyclic di-GMP signalling may afford strategies for inhibition of biofilm formation and virulence factor synthesis in bacterial pathogens read more ...