Listeria monocytogenes is the causative agent of listeriosis. The Center for Disease Control estimated that about 1,600 people get listeriosis each year, with mortality rates up to 30% in clinical cases. Listeria outbreaks have been associated with a wide variety of food products, including dairy products, produce, and ready-to-eat packaged foods. L. monocytogenes is an invasive pathogen, and can infect many organs in humans and more than forty animal species. Immunocompromised individuals face a higher risk of systemic infection and meningitis. In pregnant women, L. monocytogenes crosses the placenta to infect the fetus, causing spontaneous abortion or stillbirth.
L. monocytogenes was the first living organism found to synthesize and secrete c-di-AMP. L. monocytogenes is a long-studied model for intracellular pathogens that infect phagocytic and non-phagocytic cells. L. monocytogenes rapidly replicates in the host cytosol and spreads to neighboring cells to avoid host immunity. During intracellular growth, L. monocytogenes secretes c-di-AMP, which triggers robust type I interferon response by infected host cells. C-di-AMP is also secreted by broth cultures, but the roles for this secretion are unclear.
L. monocytogenes requires c-di-AMP for growth in rich broth media and successful infection. Mutants depleted for c-di-AMP are greatly diminished for growth, highly susceptible to cell wall-acting antibiotics, and severely attenuated for virulence. Interesting, mutants that accumulate c-di-AMP are also attenuated and stress sensitive. We currently investigate the molecular mechanisms both for c-di-AMP essentiality and toxicity in L. monocytogenes growth and infection. We also plan to develop novel antimicrobials and adjuvants based on perturbation of c-di-AMP levels within bacterial cytoplasm.