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oai:digital.lib.washington.edu:1773/471092026-02-15T21:17:21Zcom_1773_4888col_1773_4943

Salama, Nina R Jackson, Laura 2021-07-07T20:04:03Z 2021-07-07 2021 Jackson_washington_0250E_22639.pdf http://hdl.handle.net/1773/47109 Thesis (Ph.D.)--University of Washington, 2021 Helicobacter 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. application/pdf en_US CC BY bacterial evolution genetic diversity Helicobacter pylori pathogen pathogenesis within host Microbiology Cellular biology Molecular biology Molecular and cellular biology Examination of the phenotypic impacts of Helicobacter pylori diversification within a single host Thesis Delay release for 1 year -- then make Open Access 2022-07-07T20:04:03Z open.access