Genomic variation and evolution of Helicobacter pylori in Cape Verde

Helicobacter pylori (H. pylori) are humans’ stomach-dwelling bacteria that pose high mutation and recombination rates. These features allow them to achieve great genetic diversity and adapt to a wide range of within-host environments with different selective pressures, including presence of antibiotics. This study focused on the H. pylori population in Cape Verde, an archipelago that was first inhabited in the 15th century by Portuguese colonists and African slaves, followed by their extensive admixture. The high prevalence of H. pylori infection and crowded living environment facilitate cross infection and genetic exchange between divergent strains, which promote rapid evolution of the bacteria. This thesis aimed to study between-host and within-host genomic variation and evolution of H. pylori from asymptomatic individuals in Cape Verde. The genetic architecture and evolution of antibiotic resistance of H. pylori in Cape Verde were also investigated.

Population genetic analyses based on whole genome data discovered that the main axis of genetic variation of H. pylori in Cape Verde was not due to admixture as in their hosts, but presence of four populations groups, two of which were highly differentiated from African and European ancestral strains and were likely to represent recent clonal expansions. Evidence of within-host genetic exchange through recombination was found between strains within-host, regardless of the presence of multiple strains, the presence of mixed ancestry and the ancestry/ancestry combinations. Resistance mechanisms of four antibiotics (Amoxicillin, Clarithromycin, Metronidazole and Tetracycline) of H. pylori in Cape Verde were only partially explained by known resistance-associated mutations. Significantly associated variants identified using GWASs included both established and novel variants.

The understanding of this H. pylori population from asymptomatic hosts will serve as a major step towards establishment of Cape Verde as a model population for studying co-evolutionary trajectories of human hosts and bacteria.