Cyclic diguanylate (c-di-GMP) (c-di-GMP)

Cyclic diguanylate (c-di-GMP) is a ubiquitous second messenger in bacteria that plays a central role in regulating the transition between motile, planktonic states and sessile, biofilm-forming states [1, 2]. It controls various physiological processes, including virulence factor production, cell cycle progression, and the formation of multicellular communities [2]. In mammalian systems, c-di-GMP is recognized as a pathogen-associated molecular pattern (PAMP) by the innate immune sensor Stimulator of Interferon Genes (STING) [3]. Upon binding to STING, c-di-GMP induces a conformational change that activates the TBK1-IRF3 signaling axis, leading to the robust production of Type I interferons and pro-inflammatory cytokines [4]. This immunostimulatory property has positioned c-di-GMP and its synthetic analogs as promising candidates for vaccine adjuvants and cancer immunotherapies designed to convert "cold" tumors into "hot" ones [4]. However, therapeutic use is challenged by the molecule's high polarity, which limits membrane permeability, and its susceptibility to degradation by phosphodiesterases [1].

Other names

Cyclic di-GMP3',5'-cyclic diguanylic acidc-di-GMPCyclic diguanosine monophosphatec-GpG

Agonism of the Stimulator of Interferon Genes (STING) receptor, leading to Type I interferon production.