SITE-SPECIFIC DNA RECOMBINASE AND A/E PATHOGEN VIRULENCE

Project SummaryFoodborne disease is an important health threat and an immense economic burden worldwide. One importantcategory of causative agents of foodborne diseases is attaching and effacing (A/E) pathogens, which includehuman pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC) and theirmurine equivalent Citrobacter rodentium (CR). A/E pathogens share most of their genes and pathogenicmechanisms to subvert host signaling pathways and immune responses. Particularly, increasing number ofstudies demonstrate that A/E pathogen infections cause more severe morbidity and mortality inimmunocompromised hosts. However, the critical host-pathogen interactions in the gut and the mechanism(s)through which A/E pathogens suppress host immune responses have not been fully understood, especiallyunder immunocompromised condition. Our recent studies demonstrate that a novel site-specific DNArecombinase (Ssr) plays a crucial role in CR infection-caused severe morbidity and mortality inimmunocompromised animals. This project aims to elucidate the pathogenic role of Ssr in CR infection-induced pathogenesis in immunocompromised hosts and the relevance of Ssr in human A/E pathogens. Thus,we will assess the impact of Ssr on colonic inflammatory response and epithelial integrity during A/E pathogeninfections in Aim 1 and elucidate the molecular mechanism(s) through which Ssr affects virulence geneexpression during A/E pathogen infections in Aim 2. At the conclusion of these studies, we will provide novelinsights into the complex foodborne pathogenesis whereby A/E pathogen virulence is elegantly regulatedduring infections. It will also advance our understanding of the sophisticated pathogen-host interactions thatmay lead to novel strategies for prevention and treatment of A/E pathogen infections and foodborne diseases,especially under immunocompromised conditions.