Grant: Project Grant

Microbes that are resistant to antibiotics kill millions of people a year. There is an urgent need for new therapies. My research aims to uncover new knowledge about how microbes colonize and infect humans. We study bacteria that invade the gastrointestinal (GI) tract, including the number one cause of antimicrobial resistant infectious deaths, E. coli. Microbes that colonize and infect the gut must adapt to many potentially lethal stresses in order to survive, and my group has extensively characterized one pathway involved in this process, the Cpx envelope stress response. We showed that the Cpx pathway regulates the expression of bacterial factors necessary to cause disease. Recently, we made the exciting discovery that growing Cpx mutants of the model mouse pathogen Citrobacter rodentium in the lab under conditions that mimic the GI tract resulted in growth defects like those seen in animal models of infection. Bacteria in the gut are surrounded by many other microbes. We established competition assays in the lab and uncovered that the envelope stress responses of gut microbes alter their ability to compete and grow. The work outlined in this proposal will capitalize on these findings to investigate the roles of other stress responses in growth and competition under gut-like conditions. We will identify novel adaptive mechanisms that impact microbial disease causation using Citrobacter rodentium, and validate our findings in mouse models of infection. We will continue our work defining the signaling machinery that directs essential adaptations under these conditions in infectious microbes. We expect this work to generate new knowledge on the mechanisms used by infectious bacteria to colonize our guts that will be useful in sparking the design of new interventions capable of treating antimicrobial resistant infections.