Evaluating the potency of zoliflodacin against Helicobacter pylori: In vitro activity and conserved GyrB target
Jing Liu
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorJia Jia
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorTing Shi
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorYuefan Bai
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Yanqiang Huang
Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorCorresponding Author
Liping Zeng
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorCorresponding Author
Hongkai Bi
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorJing Liu
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorJia Jia
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorTing Shi
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorYuefan Bai
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Search for more papers by this authorCorresponding Author
Yanqiang Huang
Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorCorresponding Author
Liping Zeng
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorCorresponding Author
Hongkai Bi
Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China
Changzhou Medical Center, The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
Correspondence
Hongkai Bi and Liping Zeng, Jiangsu Key Laboratory of Pathogen Biology, Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Email: hkbi@njmu.edu.cn and lpzeng@njmu.edu.cn
Yanqiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise, Guangxi, China.
Email: hyq77615@163.com
Search for more papers by this authorJing Liu and Jia Jia contributed equally to this article.
Abstract
Background
The current standard treatment for Helicobacter pylori infection, which involves a combination of two broad-spectrum antibiotics, faces significant challenges due to its detrimental impact on the gut microbiota and the emergence of drug-resistant strains. This underscores the urgent requirement for the development of novel anti-H. pylori drugs. Zoliflodacin, a novel bacterial gyrase inhibitor, is currently undergoing global phase III clinical trials for treating uncomplicated Neisseria gonorrhoeae. However, there is no available data regarding its activity against H. pylori.
Materials and Methods
We evaluated the in vitro activity of zoliflodacin against H. pylori clinical isolates (n = 123) with diverse multidrug resistance. We performed DNA gyrase supercoiling and microscale thermophoresis assays to identify the target of zoliflodacin in H. pylori. We analyzed 2262 H. pylori whole genome sequences to identify Asp424Asn and Lys445Asn mutations in DNA gyrase subunit B (GyrB) that are associated with zoliflodacin resistance.
Results
Zoliflodacin exhibits potent activity against all tested isolates, with minimal inhibitory concentration (MIC) values ranging from 0.008 to 1 μg/mL (MIC50: 0.125 μg/mL; MIC90: 0.25 μg/mL). Importantly, there was no evidence of cross-resistance to any of the four first-line antibiotics commonly used against H. pylori. We identified GyrB as the primary target of zoliflodacin, with Asp424Asn or Lys445Asn substitutions conferring resistance. Screening of 2262 available H. pylori genomes for the two mutations revealed only one clinical isolate carrying Asp424Asn substitution.
Conclusion
These findings support the potential of zoliflodacin as a promising candidate for H. pylori treatment, warranting further development and evaluation.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no competing interests.
Supporting Information
| Filename | Description |
|---|---|
| hel13075-sup-0001-supinfo.docxWord 2007 document , 2.1 MB |
Data S1. Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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