Managing dangerous liaisons: lessons from <i>Helicobacter pylori</i> for understanding bacterial carcinogenesis

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