Identification and Characterization of CdgB, a Diguanylate Cyclase Involved in Developmental Processes in Streptomyces coelicolor

Abstract

We describe the identification and functional characterization of cdgB (SCO4281), a recently discovered target of BldD, a key regulator of morphological differentiation and antibiotic production in the mycelial bacteria of the genus Streptomyces. cdgB (cyclic dimeric GMP [c-di-GMP] B) encodes a GGDEF-containing protein that has diguanylate cyclase activity in vitro. Consistent with this enzymatic activity, heterologous expression of cdgB in Escherichia coli resulted in increased production of extracellular matrix in colonies and enhanced surface attachment of cells in standing liquid cultures. In Streptomyces coelicolor, both overexpression and deletion of cdgB inhibited aerial-mycelium formation, and overexpression also inhibited production of the antibiotic actinorhodin, implicating c-di-GMP in the regulation of developmental processes in Streptomyces.

Cyclic Di-GMP Phosphodiesterases RmdA and RmdB Are Involved in Regulating Colony Morphology and Development in Streptomyces coelicolor

“…Our study, along with those of Buttner and colleagues (17,59), reveals an apparently conserved function of c-di-GMP signaling in modulation of development in actinomycetes. This extends the realm of processes controlled by c-di-GMP and suggests that future studies in the Gram-positive bacteria may result in new, yet-unanticipated processes controlled by this second messenger, new kinds of c-di-GMP receptors, and new regulatory mechanisms.…”

“…Recent experiments by the Buttner group showed that overexpression of S. coelicolor DGCs encoded by cdgA or cdgB (SCO4281) block aerial mycelium formation (17,59), i.e., produce the same bald phenotype as does the rmdA rmdB double mutant. It is likely that RmdA and RmdB counterbalance the effects of CdgA and CdgB.…”

“…The c-di-GMP signaling pathways are present in many Gram-positive bacteria (9), but functional studies have been done only in mycobacteria, where c-di-GMP signaling appears to play a relatively limited role and is involved in long-term survival (32). Recent reports uncovered the involvement of c-di-GMP in the development of the Gram-positive actinomycete Streptomyces coelicolor (17,59).…”

Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger

“…Overexpression of yet another DGC, CdgB (SCO4281), resulted in the impaired formation of aerial mycelium. It is peculiar that the cdgB deletion also showed impaired hypha formation (323). Two EAL domain PDEs, RmdA (SCO0928) and RmdB (SCO5495), were also identified as responsible for hypha formation.…”

Functional Characterization of Core Components of the Bacillus subtilis Cyclic-Di-GMP Signaling Pathway

“…The first diguanylate cyclase identified in Gram-positive bacteria was Mycobacterium smegmatis MSDGC-1, a protein with both DGC activity and PDE activity in vitro (17,18). More recently, additional c-di-GMP signaling components have been characterized in M. smegmatis (19), Mycobacterium tuberculosis (20), Streptomyces coelicolor (21)(22)(23), and Clostridium difficile (15,16,24,25). These studies establish c-di-GMP as a secondary messenger in Gram-positive bacteria, but until recently the possibility of c-di-GMP signaling in a widely studied Gram-positive model organism, Bacillus subtilis, had not been reported (26).…”