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Bacterial Genotoxin Accelerates Transient Infection-Driven Murine Colon Tumorigenesis
Yue Liu1, Kai Fu1, Eric M Wier1
1Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.
Cancer Discovery
|September 4, 2021
Summary
UshA, a novel bacterial genotoxin from attaching/effacing (A/E) pathogens, directly digests DNA. This toxin accelerates colon tumor development even during transient infections, impacting colon cancer risk.
Area of Science:
- Microbiology
- Molecular Biology
- Oncology
Background:
- Chronic inflammation from persistent bacterial infections is linked to colon cancer.
- The role of transient bacterial infections in colon tumorigenesis is unclear.
Purpose of the Study:
- To identify novel bacterial factors contributing to colon tumorigenesis.
- To investigate the role of UshA in attaching/effacing (A/E) pathogens during colon cancer development.
Main Methods:
- Investigated UshA's genotoxic and DNA digestion activities.
- Examined UshA's role in host cell DNA damage and transformation via type III secretion system (T3SS).
- Assessed UshA's impact on colon tumorigenesis in a mouse model (ApcMinΔ716/+ mice).
Main Results:
- Identified UshA as a novel genotoxin in A/E pathogens with direct DNA digestion activity.
- Demonstrated UshA injection via T3SS causes host cell DNA damage and tumorigenic transformation.
- Showed UshA is essential for Citrobacter rodentium infection-accelerated colon tumorigenesis in susceptible mice.
Conclusions:
- UshA acts as a T3SS-dependent genotoxin, accelerating colon tumorigenesis during transient bacterial infections.
- Acute, noninvasive infections with A/E pathogens can significantly impact colon cancer development.
