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Photo of Dr. Fengyi Wan. He has wire-framed glasses and dark hair and is wearing a blue shirt with contrasting blue tie.

Biochemistry Seminar: Dr. Fengyi Wan (Johns Hopkins University), "Transient bacterial infection and colonic tumorigenesis"

Event Type
Department of Biochemistry (HOST: Dr. Lin-Feng Chen)
Charles G. Miller Auditorium, B102 Chemical and Life Sciences Laboratory
Apr 21, 2023   12:00 pm  
Professor, Fengyi Wan
Cara Day / Faculty Host: Lin-Feng Chen
Originating Calendar
Biochemistry Department Seminars

ABSTRACT: Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which include the human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine–aspartic acid dyad. Injected via the type III secretion system (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection–accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependent genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection–accelerated colon tumorigenesis in mice.

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