Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide.

Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide (HS, n⩾2), not organic polysulfides. Studies on the mechanism of action (MoA) show that HS specifically inactivates H. pylori glucose-6-phosphate dehydrogenase (G6PDH) by interfering with electron transfer from glucose-6-phosphate (G6P) to nicotinamide adenine dinucleotide phosphate (NADP). However, low HS yield makes garlic derivatives hard to be a reliable donor of HS to treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into FeS that generates HS with a 25-58 times increase in yield. Through chitosan encapsulation, we designed a gastric-adaptive HS microreactor (GAPSR) that eradicates H. pylori with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid H. pylori eradication than combined antibiotics therapy without disturbing the gut microbiota. These findings indicate a distinct MoA transformation mediated by polysulfide as an alternative candidate to treat H. pylori infection.