Metabolism of bile acid utilizing gut-associated anaerobic bacteria:

Understanding the metabolism of anaerobic gut microbes at the molecular level is essential, as the metabolic functions of these microbes shape the gut environment and influence human health. We focus on understanding the energy metabolism of the highly prevalent bile acid utilizing- gut-associated actinobacterium Eggerthella lenta. It is an essential member of bile acid oxidizing bacteria in the human gut that has a broad impact on the metabolism of drugs, dietary bioactives, and endogenous compounds; and it is linked to bacteremia and other chronic diseases such as colon cancer, liver cancer, and cholesterol gallstone disease. There is a need to understand the cellular metabolism, and we will define the role of the membrane-bound energy-yielding/Na+/H+ pumping Fdx: NAD oxidoreductase (Rnf) complex of E. lenta in bile-acid metabolism. The focus is to define the role of redox cofactors of the multi-subunits Rnf complex in energy metabolism. Rnf catalyzed redox reactions, the pathway of electron transfer through these cofactors determining which of these electron transfer steps are linked to energy conservation. The scope of this research is to characterize the Rnf complex that will be important drug candidate. The ultimate goal is to develop inhibitors.