Abstract
Understanding the transition of bacterial species from commensal to pathogen, or vice versa, is a key application of evolutionary theory to preventative medicine. This requires working knowledge of the molecular interaction between hosts and bacteria, ecological interactions among microbes, spatial variation in bacterial prevalence or host life history, and evolution in response to these factors. However, there are very few systems for which such broad datasets are available. One exception is the gram-negative bacterium, Helicobacter pylori, which infects upwards of 50% of the global human population. This bacterium is associated with a wide breadth of human gastrointestinal disease, including numerous cancers, inflammatory disorders, and pathogenic infections, but is also known to confer fitness benefits to its host both indirectly, through interactions with other pathogens, and directly. Outstanding questions are therefore why, when, and how this bacterium transitions along the parasitism-mutualism continuum. We examine known virulence factors, genetic predispositions of the host, and environmental contributors that impact progression of clinical disease and help define geographical trends in disease incidence. We also highlight the complexity of the interaction and discuss future therapeutic strategies for disease management and public health in light of the longstanding evolutionary history between the bacterium and its human host.