ヘリコバクター・ピロリのH2代謝がCagA移行を促進することで胃発がんに関与する機序の解明
Helicobacter pylori strain 7.13, a carcinogenic derivative, displays markedly elevated hydrogenase activity compared with its non-carcinogenic parent strain B128, and shows enhanced translocation of the CagA cytotoxin into human gastric epithelial AGS cells. Deletion of hydrogenase genes (Δhyd mutant) substantially reduced CagA delivery without affecting bacterial adhesion. Inhibition of the H2-dependent respiratory chain with the quinone reductase inhibitor HQNO similarly suppressed CagA translocation, indicating that the transmembrane potential generated by H2 oxidation drives toxin transport. The Δhyd strain also exhibited reduced DNA transformation frequency, implicating hydrogenase in energizing the DNA uptake machinery. In a gerbil infection model, the Δhyd strain induced significantly less gastric inflammation at 12 weeks post-inoculation; gastric cancer arose in 50% of wild-type-infected animals but in none infected with the Δhyd strain. Clinical H. pylori isolates from cancer patients (n=6) showed significantly higher H2/O2 hydrogenase activity than isolates from gastritis patients (n=6), supporting a link between bacterial hydrogen metabolism and gastric cancer risk in humans.
H. pylori hydrogenase oxidizes molecular hydrogen to generate a transmembrane electrochemical potential, which energizes the type IV secretion system responsible for translocating the CagA carcinogenic toxin into host gastric epithelial cells.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/27531909