Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments.
Noto JM, Chopra A, Loh JT, Romero-Gallo J, Piazuelo MB, Watson M, Leary S, Beckett AC, Wilson KT, Cover TL, Mallal S, Israel DA, Peek RM
Gut. 10 2018. doi: 10.1136/gutjnl-2017-313863
COMMENT: Helicobacter pylori is the strongest risk factor for gastric cancer but the pathogenesis appears to depend on bacterial and microenvironmental factors. In this study two carcinogenic microenvironmental factors of the host, iron deficiency and high salt intake, have been analyzed searching for the SNPs that arised in Helicobacter pylori in those two conditions.
In animal studies with Mongolian gerbils whole genome sequencing of Helicobacter pylori strains B128 and 7.13 and in vivo-adapted 7.13 output isolates harvested from animals maintained on iron-replete, iron-depleted, regular salt or high salt diets identified a small number of common polymorphisms that occurred within the context of iron deficiency and high salt intake carcinogenic microenvironments. A SNP within fur (FurR88H) that was selected after only 5 days of exposure to low iron or high salt was especially interesting and was selected to be studied in humans. For that fur was sequenced in 339 clinical Helicobacter pylori strains obtaining these results:
Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034).
Fur protein controls bacterial iron homeostasis playing an important role in bacterial metabolism, energy production and immune regulation. It is possible that the detected SNP FurR88H increases the fitness of Helicobacter pylori in low iron conditions and improves its capacity of survival and persistence within the host.
The authors conclude:
These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis