Microbial Cyclic GMP-AMP Signaling Pathways

Abstract

Cyclic dinucleotides are key second messengers essential for bacteria to adapt and thrive in different environments. The recently identified bacterial cyclic dinucleotide second messenger, 3′,3′-cyclic GMP-AMP (cGAMP), was first discovered in Vibrio cholerae. A cGAMP isomer is also found in eukaryotes, and most of the current research on cGAMP biology is focused on its role in mammalian innate immunity regulation. In contrast, how cGAMP regulates its targets and the physiological roles of cGAMP signaling in bacteria are not well understood. Here, we summarize our current knowledge of microbial cGAMP signaling pathways. We review how this unique second messenger was discovered in the current pandemic strains of V. cholerae and how the first bacterial cGAMP protein target was identified. We discuss the potential roles of cGAMP signaling in membrane metabolism, gene regulation, pathogenesis, and evolution of V. cholerae as well as in other bacteria. We also compare the similarities and differences in microbial and eukaryotic cGAMP signaling pathways. Finally, we discuss the outlook of microbial cGAMP signaling research in the context of basic microbiology as well as in studying host–pathogen interactions.