Examination of the phenotypic impacts of Helicobacter pylori diversification within a single host

Thesis (Ph.D.)--University of Washington, 2021Helicobacter pylori, one of the most common bacterial pathogens colonizing humans, is the main agent responsible for stomach ulcers and cancer. Certain strain types are associated with increased risk of disease, however many factors contributing to disease outcome remain unknown. Prior work has documented genetic diversity among bacterial populations within single individuals, but the impact of this diversity for continued bacterial infection or disease progression remains understudied. In our analysis we examined both genetic and functional features of many stomach isolates from a single individual infected over six years. During these six years the subject shifted from having excess acid production and a duodenal ulcer to lower acid production from gastric atrophy. The 39 isolates form sub-populations based on gene sequence changes that accumulated in the different isolates. In addition to having distinguishing genetic features, these sub-populations also have differences in several bacterial properties, including cell shape, motility, ability to activate immune responses, and colonization in healthy mice and a mouse model of metaplasia. This apparent functional specialization suggests that the bacterial sub-populations may have adapted to distinct niches within the stomach during chronic infection. However, in this patient we find subgroups with distinct genotypic and phenotypic properties cluster independently from the stomach region from which they were isolated