The bacterial signaling molecules cyclic diguanosine monophosphate (c-di-GMP, 6a) and cyclic diadenosine monophosphate (c-di-AMP, 6b) are both key second messengers (Gomelsky, M., cAMP, c-di-GMP, c-di-AMP and now cGMP: Bacteria use them all, Mol. Microbiol. 2011, 79, 562-565; Römling, U., Great times for small molecules: c-di-AMP, a second messenger candidate in bacteria and archaea. Sci. Signal. 2008, 1, pe39). Because of their critical functions in essential bacterial pathways, c-di-GMP and c-di-AMP have major implications for human health. However, in spite of advances in the identification of proteins and RNA to which c-di-GMP and c-di-AMP bind, a great many additional receptors remain unknown (Galperin, M. Y.; Higdon, R.; Kolker, E., Interplay of heritage and habitat in the distribution of bacterial signal transduction systems. Mol. BioSyst. 2010, 6, 721-728). New tools are needed to determine the roles c-di-GMP and c-di-AMP have in human health.