Occurrence of Cyclic di-GMP-Modulating Output Domains in Cyanobacteria: an Illuminating Perspective

Abstract

Microorganisms use a variety of metabolites to respond to external stimuli, including second messengers that amplify primary signals and elicit biochemical changes in a cell. Levels of the second messenger cyclic dimeric GMP (c-di-GMP) are regulated by a variety of environmental stimuli and play a critical role in regulating cellular processes such as biofilm formation and cellular motility. Cyclic di-GMP signaling systems have been largely characterized in pathogenic bacteria; however, proteins that can impact the synthesis or degradation of c-di-GMP are prominent in cyanobacterial species and yet remain largely underexplored. In cyanobacteria, many putative c-di-GMP synthesis or degradation domains are found in genes that also harbor light-responsive signal input domains, suggesting that light is an important signal for altering c-di-GMP homeostasis. Indeed, c-di-GMP-associated domains are often the second most common output domain in photoreceptors—outnumbered only by a histidine kinase output domain. Cyanobacteria differ from other bacteria regarding the number and types of photoreceptor domains associated with c-di-GMP domains. Due to the widespread distribution of c-di-GMP domains in cyanobacteria, we investigated the evolutionary origin of a subset of genes. Phylogenetic analyses showed that c-di-GMP signaling systems were present early in cyanobacteria and c-di-GMP genes were both vertically and horizontally inherited during their evolution. Finally, we compared intracellular levels of c-di-GMP in two cyanobacterial species under different light qualities, confirming that light is an important factor for regulating this second messenger in vivo.

Regulation of biofilm formation and cellular buoyancy through modulating intracellular cyclic di‐GMP levels in engineered cyanobacteria

“…After demonstrating that c‐di‐GMP can trigger biofilm formation and aggregation, we hypothesized that BL‐grown WT Synechocystis cells exhibiting high c‐di‐GMP levels could produce biofilm and cells could aggregate. Previously, we showed that c‐di‐GMP levels in Synechocystis are three times higher under BL compared to WL and red light (RL), and almost twice as much when compared to cells under green light (GL) (Agostoni et al, ). When maintained under BL, Synechocystis indeed produced biofilm in an adhesive layer on the bottom of flasks and it was easily perceived by eye (Fig.…”

A Symphony of Cyclases: Specificity in Diguanylate Cyclase Signaling

“…These residues include RXXD, called the primary I-site, which acts to bind c-di-GMP and quell the enzyme’s catalytic activity while bound (Figure 2). The GGDEF domain may exist independently, or it may be fused to a variety of other domains, including PAS, CACHE, CHASE, MASE, and response regulator domains (1, 18, 23). PDEs that break down c-di-GMP come in two varieties.…”

Three cyanobacteriochromes work together to form a light color-sensitive input system for c-di-GMP signaling of cell aggregation

“…PCC 6803 genes encoding these domains (16,19). Many of the c-di-GMP synthesis/degradation proteins have been shown to be specifically involved in a particular response pathway, owing to, for example, transcriptional regulation, protein-protein interaction(s), and variation in the binding affinity of c-di-GMP receptors for c-di-GMP (16).…”

“…C-di-GMP is universally found in bacteria, including cyanobacteria, and generally induces sessile multicellular lifestyles and represses motility in these organisms (16). It seems that light is a major factor regulating c-di-GMP signaling (5,8,(17)(18)(19). The GGDEF domain usually synthesizes c-di-GMP via its diguanylate cyclase (DGC) activity (20), whereas the EAL and HD-GYP domains usually degrade c-di-GMP via their phosphodiesterase (PDE) activities (21,22).…”