A community-driven genomic investigation of Helicobacter pylori isolates from Indigenous communities in the Arctic of Canada.

Helicobacter pylori is a Gram-negative, flagellate, microaerophilic member of the Epsilonproteobacteria, with a spiral or curved bacilli morphology (Marshall and Warren 1984). The bacterium resides in the human stomach, and infections can span decades, often going undetected due to minor pathogenesis (Kusters et al. 2006). Infections frequency is higher in the Global South, and is associated with low socioeconomic status, education, remoteness, and inaccessibility to healthcare (Hooi et al. 2017; Bruce and Maaroos 2008). This infection is a public health concern because H. pylori infection increases the risk of adenocarcinoma of the gastric mucosa and gastric B-cell mucosal-associated lymphoid tissue (MALT) lymphoma, as well as peptic ulcer disease (Haley and Gaddy 2015). Indigenous communities in Canada experience increased rates of H. pylori infection, which is associated with poverty, crowded living conditions, and inaccessible health care. Infection is a concern for Indigenous communities given the bacterium's implication in the development of associated cancers, which is a severe health burden that too disproportionately affects Indigenous peoples. This project builds upon ongoing community-driven research by the Canadian North H. pylori (CANHelp) Working Group investigating the impact of H. pylori infection. In this research project we present the sequence H. pylori genomes of 57 CANHelp isolates sampled from the Western Canadian Arctic communities of Aklavik, Inuvik, Old Crow, Ross River, Teslin, and Fort McPherson and a comparator cohort of 73 southern Manitoban isolates. I developed and implemented a contamination detection pipeline to ensure only H. pylori sequence reads were used in genome assembly. The genomes were analyzed for their presence of: known markers associated with antimicrobial resistance to clarithromycin, metronidazole, levofloxacin, and amoxicillin; virulence factors like cagA, the cagPI, vacA, outer membrane proteins such as babA, and the Type I toxin-antitoxin system aapA1/isoA1; and the presence of mobile genomic elements such as plasmids, prophages, and genomic islands. The phylogenetic structure of these isolates was determined and explored, including determining genome sequence type, admixture, and patterns based on host household structures. Manitoban genomes were predominantly European in sequence type and were more likely to carry genetic features associated with virulence and antimicrobial resistance. Several distinct clades of CANHelp genomes were identified. Most notable were clades containing isolates belonging to a North American Indigenous sequence type. These genomes were less likely to carry genetic features associated with virulence and antimicrobial resistance. They were also smaller in genome length and in the number of coding sequences and were predominantly from Aklavik. This absence of genetic features was especially apparent when these genomes were compared to other CANHelp genomes belonging to European and African sequence types, which were more likely to carry these virulence- and resistance-associated features. These results suggest that there may be distinct H. pylori strains circulating in CANHelp communities with variable impact on hosts, including resistance to treatment. This project represents the first step in fully characterizing nearly 300 H. pylori isolates collected by the CANHelp Working Group.

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