Abstract 2281 Discovery of divergent activity in cyclic dinucleotide signaling

Cyclic dinucleotides are signaling molecules that have been found in all three domains of life. In the past decade, our understanding of this class of signals has greatly expanded with the discovery of novel signals as well as novel functions. The signal cGAMP is the only cyclic dinucleotide involved in two separate signaling pathways in bacteria, with not only different enzymes and effectors but also distinct physiological functions in innate immunity and transient surface-associated phenotypes. Intriguingly, one of these pathways appears to have arisen from divergent evolution of components of the more widespread cyclic di-GMP signaling pathway. Here I will discuss our latest findings about this 'divergent' pathway, from the discovery of signaling phosphodiesterases that act specifically on cGAMP, novel surface-associated phenotypes, and the first evidence for a synthase enzyme capable of switching the cyclic dinucleotide signal it produces. In addition, I will provide an update on development and application of biosensor tools to elucidate and study the primary inputs that regulate cyclic dinucleotide signaling. This research has been supported by grants from the National Institutes of Health (R01 GM124589), National Science Foundation (NSF-BSF 1815508), and Sorenson Legacy Fund.