{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:01:44Z","timestamp":1791414104545,"version":"4.3.3"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFC0311003"],"award-info":[{"award-number":["2018YFC0311003"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073899, 82202531"],"award-info":[{"award-number":["82073899, 82202531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The current standard treatment for <jats:italic>Helicobacter pylori<\/jats:italic> infection, which involves a combination of two broad\u2010spectrum antibiotics, faces significant challenges due to its detrimental impact on the gut microbiota and the emergence of drug\u2010resistant strains. This underscores the urgent requirement for the development of novel anti\u2010<jats:italic>H. pylori<\/jats:italic> drugs. Zoliflodacin, a novel bacterial gyrase inhibitor, is currently undergoing global phase III clinical trials for treating uncomplicated <jats:italic>Neisseria gonorrhoeae<\/jats:italic>. However, there is no available data regarding its activity against <jats:italic>H<\/jats:italic>. <jats:italic>pylori<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>We evaluated the in\u00a0vitro activity of zoliflodacin against <jats:italic>H. pylori<\/jats:italic> clinical isolates (<jats:italic>n<\/jats:italic>\u2009=\u2009123) with diverse multidrug resistance. We performed DNA gyrase supercoiling and microscale thermophoresis assays to identify the target of zoliflodacin in <jats:italic>H. pylori<\/jats:italic>. We analyzed 2262 <jats:italic>H. pylori<\/jats:italic> whole genome sequences to identify Asp424Asn and Lys445Asn mutations in DNA gyrase subunit B (GyrB) that are associated with zoliflodacin resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Zoliflodacin exhibits potent activity against all tested isolates, with minimal inhibitory concentration (MIC) values ranging from 0.008 to 1\u2009\u03bcg\/mL (MIC<jats:sub>50<\/jats:sub>: 0.125\u2009\u03bcg\/mL; MIC<jats:sub>90<\/jats:sub>: 0.25\u2009\u03bcg\/mL). Importantly, there was no evidence of cross\u2010resistance to any of the four first\u2010line antibiotics commonly used against <jats:italic>H. pylori<\/jats:italic>. We identified GyrB as the primary target of zoliflodacin, with Asp424Asn or Lys445Asn substitutions conferring resistance. Screening of 2262 available <jats:italic>H. pylori<\/jats:italic> genomes for the two mutations revealed only one clinical isolate carrying Asp424Asn substitution.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings support the potential of zoliflodacin as a promising candidate for <jats:italic>H. pylori<\/jats:italic> treatment, warranting further development and evaluation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hel.13075","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T04:50:48Z","timestamp":1713329448000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluating the potency of zoliflodacin against <i>Helicobacter pylori<\/i>: In\u00a0vitro activity and conserved <scp>GyrB<\/scp> target"],"prefix":"10.1111","volume":"29","author":[{"given":"Jing","family":"Liu","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Changzhou Medical Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Jia","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Changzhou Medical Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Shi","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Changzhou Medical Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuefan","family":"Bai","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Changzhou Medical Center The Affiliated Changzhou Second People's Hospital of Nanjing Medical University  Changzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0867-0178","authenticated-orcid":false,"given":"Yanqiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance Youjiang Medical University for Nationalities  Baise Guangxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Zeng","sequence":"additional","affiliation":[{"name":"Jiangsu Key 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