Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide  

作　　者：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 

机构地区：[1]CAS Engineering Laboratory for Nanozyme,Key Laboratory of Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing,100101,China [2]School of Life Sciences,University of Chinese Academy of Sciences,Beijing,100101,China [3]College of Chemistry and Chemical Engineering,Jiangxi Normal University,Nanchang,330022,China [4]Key Laboratory of Epigenetic Regulation and Intervention,Institute of Biophysics,Chinese Academy of Sciences,Beijing,100101,China [5]Nanozyme Laboratory in Zhongyuan,School of Basic Medical Sciences,Zhengzhou University,Zhengzhou,450001,China [6]Nanozyme Laboratory in Zhongyuan,Henan Academy of Innovations in Medical Science,Zhengzhou,451163,China

出　　处：《Science China(Life Sciences)》2025年第4期1158-1173,共16页中国科学(生命科学英文版)

基　　金：supported by the National Key R&D Program of China(2019YFA0709200);the National Natural Science Foundation of China(22121003,81930050)。

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(H_(2)S_(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 H_(2)S_(n)yield makes garlic derivatives hard to be a reliable donor of H_(2)S_(n)to treat H.pylori infection.To address this challenge,we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4that generates H_(2)S_(n)with a 25–58 times increase in yield.Through chitosan encapsulation,we designed a gastric-adaptive H_(2)S_(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.

关 键 词：hydrogen polysulfide G6PDH inactivation Helicobacter pylori polysulfide transformation gastric-adaptive 

分 类 号：R573[医药卫生—消化系统]