Drosophila as a model organism to understand infection tolerance mechanisms. Victoria Allen, Reed O'Connor, Clarice Zhou, Vanessa Hill, Elizabeth Stone-Jacobs, Thomas McCord, Michelle Shirasu-Hiza. Genetics and Development, Columbia University Medical Center, New York, NY.

   The rise of antibiotic-resistant strains of bacteria has led to a modern crisis in treatment of severe bacterial infection (sepsis). There are two ways the host can fight infection: resistance and infection tolerance. Resistance mechanisms limit bacterial growth; infection tolerance mechanisms help the host to endure the pathogenic effects of infection. Here we use Drosophila as a model organism to understand infection tolerance mechanisms. Our lab focuses on identifying circadian-regulated physiologies that contribute to survival of infection. We found that circadian mutants are less resistant to several types of bacterial infections and more tolerant of others. Circadian mutants have altered feeding habits; we found that short-term differences in the flies diet affect tolerance of infection. We are currently identifying specific nutrients and signaling pathways that impact infection tolerance. Our work will provide insights into the underlying mechanisms of infection tolerance and potentially new therapeutic approaches to the treatment of sepsis.