biostudies-literatureUnknown16(1)Hang XThe National Natural Science Foundation of ChinaHelicobacter pylori, a globally significant pathogen, plays a central etiological role in diverse gastric pathologies ranging from chronic gastritis and peptic ulcers to gastric adenocarcinoma. Although conventional antibiotics effectively inhibit or kill growing helical H. pylori, metabolically dormant coccoid forms of H. pylori exhibit considerable tolerance, posing a persistent and clinically significant challenge. Here, we report napabucasin (2-acetylfuro-1,4-naphthoquinone) as a redox-cycling antibiotic with potent bactericidal activity against both drug-resistant helical and coccoid forms of H. pylori. Notably, napabucasin does not induce acquired resistance in vitro and demonstrates superior efficacy compared to standard triple therapy in murine infection models. Mechanistic studiesNature communications6965https://www.ebi.ac.uk/biostudies/studies/S-EPMC12307629biostudies-literature2-oxoglutarate:acceptor oxidoreductase-catalyzed redox cycling effectively targets coccoid forms of Helicobacter pylori.PMC12307629Hu STong QBi SZeng LHuang HXia QDong LZhang MShi TYanqiang HLan WBai YHang XWang JJia JBi HYang ZGao Yfalse2-oxoglutarate:acceptor oxidoreductase-catalyzed redox cycling effectively targets coccoid forms of Helicobacter pylori.Helicobacter pylori, a globally significant pathogen, plays a central etiological role in diverse gastric pathologies ranging from chronic gastritis and peptic ulcers to gastric adenocarcinoma. Although conventional antibiotics effectively inhibit or kill growing helical H. pylori, metabolically dormant coccoid forms of H. pylori exhibit considerable tolerance, posing a persistent and clinically significant challenge. Here, we report napabucasin (2-acetylfuro-1,4-naphthoquinone) as a redox-cycling antibiotic with potent bactericidal activity against both drug-resistant helical and coccoid forms of H. pylori. Notably, napabucasin does not induce acquired resistance in vitro and demonstrates superior efficacy compared to standard triple therapy in murine infection models. Mechanistic studies2025-01-01T00:00:00Z2025 Jul2026-03-18T14:04:44.508Z2025-08-23T03:07:08.419ZS-EPMC123076294073056310.1038/s41467-025-62477-4