Dietary copper reconfigures pathogen growth

Project SummaryThe vertebrate large intestine is host to a large microbial community that confers benefit byfunctioning in host nutrition, immune education and colonization resistance against entericpathogens. The composition of the gut microbiota varies with the diet, but little is known abouthow shifts in the microbiota composition affect functionality, such as the ability to confercolonization resistance against enteric pathogens. Here we will investigate how dietary coppersupplementation, a common practice to improve growth performance in livestock, alterscolonization resistance against the enteric pathogen Salmonella enterica serovar (S.)Typhimurium. Our central hypothesis is that dietary copper supplementation depletes propionate-producing Bacteroidaceae from the gut microbiota, thereby conferring a fitness advantage for S.Typhimurium strains carrying the sopE gene. We will test key aspects of our hypothesis andaccomplish the objectives of this application using the logical and innovative approach outlined inthe following specific aim: Determine whether a dietary copper-induced Bacteroidaceae depletionlowers colonization resistance against S. Typhimurium lysogenized with a sopE-encodingprophage. It is our expectation that the outcome of our experiments will show that diet-inducedshifts in the gut microbiota composition in livestock can select for enteric pathogens carrying newvirulence factors, which is relevant for human health because livestock carriage is a commonroute for introducing the pathogen into our food supply. This outcome will be significant becauseit will usher in the novel concept that diet-induced shifts in the microbiota composition can selectfor new virulence factors in enteric pathogens, a paradigm of broad interest to researchers inbacterial pathogenesis, microbiota and nutrition.