cdiAMP

cdiAMP, or cyclic di-adenosine monophosphate (c-di-AMP), is a small-molecule second messenger used by many bacteria and some archaea. It is produced by diadenylate cyclases (DACs) that convert two ATP molecules into c-di-AMP, with enzymes such as DisA and membrane-associated CdaA/DacA serving as key sources in different species. The molecule is degraded by specific phosphodiesterases, notably GdpP and related enzymes, which hydrolyze c-di-AMP to linear products and ultimately to AMP. Cellular levels of c-di-AMP are tightly regulated, and perturbations can affect growth and viability.

In bacterial cells, c-di-AMP participates in several essential processes. It is a central regulator of osmotic and ionic homeostasis, notably affecting potassium uptake through Ktr-like channels. It also influences cell wall biosynthesis and cell size, as well as responses to environmental stress, metabolism, biofilm formation, and virulence in pathogenic organisms. Many c-di-AMP targets are regulatory proteins with CBS or other sensory domains, or RNA-based elements such as riboswitches, which alter gene expression upon binding the molecule.

Receptors and signaling pathways: c-di-AMP interacts with a range of protein and RNA regulators, enabling coordination of physiological states with environmental cues. In addition to bacterial signaling, cyclic dinucleotides like c-di-AMP can be sensed by host cells via the STING pathway, leading to innate immune responses such as type I interferon production.

Because of its central role in growth, stress response, and virulence, c-di-AMP signaling is a focus of research as a potential target for antimicrobial strategies.