Grant: Operating Grant

The intestinal (digestive) tract is filled with vast numbers of microorganisms, including bacteria, viruses and other microbes. Collectively, these microbes are called the 'intestinal microbiota'. We have known about their presence for centuries, but we are only beginning to realize the large role they play in health and disease. Our laboratory has developed animal infection models using pathogenic bacteria that can cause diseases in humans, including those that cause food poisoning (called Salmonella and pathogenic E. coli, such as E. coli O157). Importantly, we demonstrated that the intestinal microbiota can alter the outcome of a disease caused by these pathogens: i.e. whether one gets sick or not. But determining how they impact on disease occurrence and outcomes is a key question, and this is the main focus of this application. We have begun to identify small molecules, either made by the microbiota or by the intestine in response to their presence, that affect the molecular machinery the microbe needs to cause disease. We will further study these molecules and how they interact with pathogenic bacteria, and determine their role in animal infection models. By understanding how the intestinal microbiota interact with Salmonella and pathogenic E. coli, we will ultimately be able to block these and other pathogenic microbes that cause much disease worldwide.