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 (H₂S_n, n⩾2), not organic polysulfides. Studies on the mechanism of action (MoA) show that H₂S_n 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 H₂S_n yield makes garlic derivatives hard to be a reliable donor of H₂S_n to treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe₃S₄ that generates H₂S_n with a 25-58 times increase in yield. Through chitosan encapsulation, we designed a gastric-adaptive H₂S_n 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.