Diguanylate cyclase (DGC) (DGC)

Diguanylate cyclases (DGCs) are a class of bacterial nucleotidyltransferase enzymes characterized by the presence of a conserved GGDEF domain (Römling et al., 2013). They play a pivotal role in bacterial physiology by synthesizing the second messenger cyclic diguanylate (c-di-GMP) from two molecules of GTP (Valentini & Filloux, 2016). High intracellular levels of c-di-GMP typically signal a transition from a motile, planktonic state to a sessile, biofilm-forming state, which protects bacteria from environmental stressors and host immune responses. Because biofilms are a major factor in chronic infections and antibiotic resistance, DGCs have emerged as attractive therapeutic targets (Opoku-Temeng et al., 2016). Inhibiting these enzymes can prevent the establishment of biofilms or trigger the dispersal of existing ones, potentially restoring the efficacy of conventional antibiotics. Current research focuses on small-molecule inhibitors that target the catalytic or allosteric sites of DGCs to modulate c-di-GMP signaling pathways.

Other names

GGDEF domain-containing proteinc-di-GMP synthaseGTP:GTP guanylyltransferase (cyclizing)Diguanidylate cyclaseCyclic di-GMP synthase

Inhibition of c-di-GMP synthesis by binding to the catalytic GGDEF domain (A-site) or the allosteric inhibitory site (I-site) of diguanylate cyclases, thereby reducing intracellular c-di-GMP levels and suppressing the transition to a biofilm-forming phenotype (Opoku-Temeng et al., 2016; Sambanthamoorthy et al., 2012).