Managing dangerous liaisons: lessons fromfor understanding bacterial carcinogenesis.

Abstract

As the first bacterium to be deemed a class I carcinogen by the World Health Organization in 1994,has paved the way for studying complex host-pathogen interactions. While 1982 marked the discovery of this helical-shaped microorganism found in gastric biopsies by Drs. Robin Warren and Barry Marshall, it took years to linkinfection to gastric inflammation, ulcers, and adenocarcinoma (recognized by a Nobel Prize in 2005). Further investigations into howcolonizes the stomach, the identification of key virulence factors (such as VacA, CagA, and outer membrane proteins), and global epidemiological studies solidified the impact ofon gastric disease. This review details the seminal discovery ofand subsequent work that cemented its status as a microbial carcinogen. Because chronicinfection and progressive changes to the tissue environment prior to cancer development can span years/decades, studyingpathogenesis has been challenging. We focus on the importance of using animal models, in particular mouse models, to recapitulate hallmarks ofdriven human disease. Finally, we highlight recent findings illustrating howhas adapted to survive and utilize oxidative stress induced during infection, which potentiates cancer development. Due to the long-lasting nature ofinfection and associated remodeling of the host environment that, in turn, promotes carcinogenesis,stands as a model organism for understanding other chronic bacterial infections in humans and pathogen-associated malignancies.