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<p>Alternative treatment for the highly prevalent <i>Helicobacter pylori</i> infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-<i>H. pylori</i> component in garlic is hydrogen polysulfide (H<sub>2</sub>S<sub><i>n</i></sub>, <i>n</i>⩾2), not organic polysulfides. Studies on the mechanism of action (MoA) show that H<sub>2</sub>S<sub><i>n</i></sub> specifically inactivates <i>H. pylori</i> glucose-6-phosphate dehydrogenase (G6PDH) by interfering with electron transfer from glucose-6-phosphate (G6P) to nicotinamide adenine dinucleotide phosphate (NADP<sup>+</sup>). However, low H<sub>2</sub>S<sub><i>n</i></sub> yield makes garlic derivatives hard to be a reliable donor of H<sub>2</sub>S<sub><i>n</i></sub> to treat <i>H. pylori</i> infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe<sub>3</sub>S<sub>4</sub> that generates H<sub>2</sub>S<sub><i>n</i></sub> with a 25–58 times increase in yield. Through chitosan encapsulation, we designed a gastric-adaptive H<sub>2</sub>S<sub><i>n</i></sub> microreactor (GAPSR) that eradicates <i>H. pylori</i> with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid <i>H. pylori</i> 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 <i>H. pylori</i> infection.</p>

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Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide

  • 期刊论文

  • 发表日期：

    2025年1月14日

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  • Xiaonan Wang,
  • Ning Zhou,
  • Xuejiao J. Gao,
  • Zijing Zhu,
  • Minmin Sun,
  • Qian Wang,
  • Haolin Cao,
  • Xuetong Wu,
  • Caiyu Zhou,
  • Qingkang Zheng,
  • Ye Yuan,
  • Yuan Liu,
  • Lei Chen,
  • Jing Jiang,
  • Pengcheng Bu,
  • Lizeng Gao

摘要

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 (H2Sn, n⩾2), not organic polysulfides. Studies on the mechanism of action (MoA) show that H2Sn 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 H2Sn yield makes garlic derivatives hard to be a reliable donor of H2Sn to treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4 that generates H2Sn with a 25–58 times increase in yield. Through chitosan encapsulation, we designed a gastric-adaptive H2Sn 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.