Managing dangerous liaisons: lessons from Helicobacter pylori for understanding bacterial carcinogenesis

As the first bacterium to be deemed a class I carcinogen by the World Health Organization in 1994, Helicobacter pylori 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 link H. pylori infection to gastric inflammation, ulcers, and adenocarcinoma (recognized by a Nobel Prize in 2005). Further investigations into how H. pylori colonizes the stomach, the identification of key virulence factors (such as VacA, CagA, and outer membrane proteins), and global epidemiological studies solidified the impact of H. pylori on gastric disease. This review details the seminal discovery of H. pylori and subsequent work that cemented its status as a microbial carcinogen. Because chronic H. pylori infection and progressive changes to the tissue environment prior to cancer development can span years/decades, studying H. pylori pathogenesis has been challenging. We focus on the importance of using animal models, in particular mouse models, to recapitulate hallmarks of H. pylori-driven human disease. Finally, we highlight recent findings illustrating how H. pylori has adapted to survive and utilize oxidative stress induced during infection, which potentiates cancer development. Due to the long-lasting nature of H. pylori infection and associated remodeling of the host environment that, in turn, promotes carcinogenesis, H. pylori stands as a model organism for understanding other chronic bacterial infections in humans and pathogen-associated malignancies.