Ronkainen, J. | Search bioRxiv

bioRxiv2023

Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabAs binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

immunology↗

bioRxiv2021

Repeated out-of-Africa expansions of Helicobacter pylori driven by replacement of deleterious mutations

Helicobacter pylori lives in the human stomach and has a population structure which resembles that of its host. However, H. pylori from Europe and the Middle East trace a substantially higher fraction of ancestry from modern African populations than the humans that carry them. Here, we used a collection of Afro-Eurasian H. pylori genomes to show that this African ancestry is due to at least three distinct admixture events. H. pylori from East Asia, which have undergone little admixture, have accumulated many more non-synonymous mutations than African strains. European and Middle Eastern bacteria have elevated African ancestry at the sites of these mutations compared to either non-segregating or synonymous sites, implying selection to remove them. We used simulations to show that demographic bottlenecks can lead to long-term segregation of deleterious mutations, despite high rates of homologous recombination, but that population fitness can be restored by migration of small numbers of bacteria from non-bottlenecked populations, leading to mosaic patterns of ancestry like that seen for H. pylori. We conclude that H. pylori have been able to spread repeatedly from Africa by outcompeting strains that carried deleterious mutations accumulated during the original out-of-Africa bottleneck.

evolutionary biology↗