Leasure Hall, Room 13 Thursday, April 21, 2016 4:00 P.M. Coffee and Cookies Leasure Hall, Room 13 alcove 3:45 P.M. iochemistry olecular iophysics The Restaurant Hypothesis of Intestinal Colonization Tyrrell Conway Microbiology and Molecular Genetics Oklahoma State University Competition for resources defines community structure and determines the success or failure of introduced species. According to David Tillman’s theory of equilibrium competition, stable co-existence of two species is possible when competing for two resources. Rolf Freter sought to understand how competition for resources in the intestine resulted in stable multispecies communities. Freter postulated that for many species to coexist each must use one limiting nutrient better than all others. According to the nutrient-niche hypothesis, successful invaders might use nutrients not used by colonized residents or outcompete them for the same nutrients. Recently, we isolated an E. coli mutant from the mouse intestine that grows 50% slower in vitro on mucus, yet is a 10-fold better colonizer than its parent, which suggests that the mutant occupies a niche that is distinct from the one occupied by its parent. We therefore postulated that E. coli resides in “restaurants” where it grows on sugars that are served locally by polysaccharide degrading anaerobes in mixed biofilms. Accordingly, the resident microbiota, which serves as a barrier to colonization by invaders, resides in mixed biofilms, taking up nutrients almost as rapidly as they are released by adjacent polysaccharide degrading anaerobes. Hence, small amounts of the sugars that escape the mixed biofilms would be available to invading pathogens. However, the invaders would have to compete directly with planktonic residents that have left the biofilms. Consequently, an invader might initially compete in a “Freter-like” niche, in which nutrients are mixed and equally available to invaders and planktonic residents alike, and if it can remain long enough in the intestine, then enter a “restaurant” and become stably colonized. Invading pathogens and commensals alike must acquire nutrients to initiate infection or engage in the succession of microorganisms that make up a stable healthy community, respectively. Understanding how enteric pathogens compete for nutrients to overcome colonization resistance is needed to prevent intestinal infections.