Abstract
Helicobacter pylori
is the dominant member of the gastric microbiota and has been associated with an increased risk of gastric cancer and peptic ulcers in adults.
H. pylori
populations have migrated and diverged with human populations, and health effects vary. Here, we describe the whole genome of the
cag
-positive strain V225d, cultured from a Venezuelan Piaroa Amerindian subject. To gain insight into the evolution and host adaptation of this bacterium, we undertook comparative
H. pylori
genomic analyses. A robust multiprotein phylogenetic tree reflects the major human migration out of Africa, across Europe, through Asia, and into the New World, placing Amerindian
H. pylori
as a particularly close sister group to East Asian
H. pylori
. In contrast, phylogenetic analysis of the host-interactive genes
vacA
and
cagA
shows substantial divergence of Amerindian from Old World forms and indicates new genotypes (e.g., VacA m3) involving these loci. Despite deletions in CagA EPIYA and CRPIA domains, V225d stimulates interleukin-8 secretion and the hummingbird phenotype in AGS cells. However, following a 33-week passage in the mouse stomach, these phenotypes were lost in isolate V225-RE, which had a 15-kb deletion in the
cag
pathogenicity island that truncated CagA and eliminated some of the type IV secretion system genes. Thus, the unusual V225d
cag
architecture was fully functional via conserved elements, but the natural deletion of 13
cag
pathogenicity island genes and the truncation of CagA impaired the ability to induce inflammation.