Research in the Woodward laboratory is focused on elucidating the interactions of bacterial pathogens with their hosts. We utilize the gram-positive intracellular bacterium Listeria monocytogenes as a genetically tractable model to define (i) the molecular features that allow access and adaptation of bacteria to the host intracellular niche and (ii) the host response to bacteria on the outcome of infection. The novel bacterial nucleotide cyclic di-AMP is recognized by the infected host during L. monocytogenes entry into the host cell cytosol. C-di-AMP is a recently discovered bacterial signaling molecule that is highly conserved among many bacteria that interact with eukaryotic hosts, although its function in these microbes generally remains unknown. We utilize a diverse array of techniques including bacterial genetics, biochemistry, mass spectrometry, proteomics, cell culture and in vivo models of infection to further interrogate the mechanisms of cytosolic immuno-surveillance as well as the roles of c-di-AMP in bacterial physiology.