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SITE-SPECIFIC DNA RECOMBINASE AND A/E PATHOGEN VIRULENCE

Investigators
Wan, Fengyi
Institutions
Johns Hopkins University
Start date
2018
End date
2020
Objective
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.
Funding Source
Nat'l. Inst. of Allergy and Infectious Diseases
Project source
View this project
Project number
1R21AI137719-01A1
Categories
Bacterial Pathogens
Escherichia coli