Bacterial Genotoxin Accelerates Transient Infection–Driven Murine Colon Tumorigenesis
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2022
- Source ID
- 10.1158/2159-8290.cd-21-0912
Entities
People
- Andrea Hodgson
- Cynthia Sears
- Dandan Zheng
- Dongqing Xu
- Eric M Wier
- Fengyi Wan
- Hua Ding
- Jian Yang
- Kai Fu
- Xue Xia
- Yifan Lei
- Yue Liu
Organizations
- American Cancer Society
- American Heart Association
- Johns Hopkins University
- National Institutes of Health
- Peking Union Medical College
- United States Department of Defense
- Willowcroft Foundation