FtsZ as a novel target for antibiotics development: Promises and challenges
Filamenting temperature-sensitive mutant Z (FtsZ), a protein essential for bacterial cell division, is highly conserved across bacterial species but absent in humans, positioning it as a strategic target for the development of antibiotics. Significant efforts to identify FtsZ inhibitors—via biochemi...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Acta Pharmaceutica Sinica B |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383525004113 |
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| author | Ming-Wei Wang Kaini Hang Wei Han Xin Li Qingtong Zhou Dehua Yang |
| author_facet | Ming-Wei Wang Kaini Hang Wei Han Xin Li Qingtong Zhou Dehua Yang |
| author_sort | Ming-Wei Wang |
| collection | DOAJ |
| description | Filamenting temperature-sensitive mutant Z (FtsZ), a protein essential for bacterial cell division, is highly conserved across bacterial species but absent in humans, positioning it as a strategic target for the development of antibiotics. Significant efforts to identify FtsZ inhibitors—via biochemical assays (e.g., GTPase activity) and cellular approaches (e.g., immunofluorescence)—have yielded over 100 natural products and synthetic compounds, whose cheminformatics clustering underscores a limited chemical diversity among the current scaffolds. Structural studies, including X-ray crystallography and cryo-electron microscopy, have resolved 97 FtsZ structures revealing conserved polymerization mechanisms and conformational plasticity, as exemplified by extremophile adaptations (e.g., Shewanella benthica from the high-pressure environment of the Mariana Trench's Challenger Deep). However, clinical translation is hindered by weak binding affinities, inhibitory inefficacy, dynamic conformational flexibility, and evolving drug resistance linked to FtsZ's functional plasticity. To address these challenges, future efforts should be directed to resolve transient assembly intermediates, leveraging machine learning with high-throughput screening, and integrating structural biology with pharmacokinetic optimization. Multidisciplinary strategies combining these approaches hold promise for translating FtsZ-focused research into clinically viable therapies, addressing the critical unmet need posed by antibiotics resistance. |
| format | Article |
| id | doaj-art-3ed3067b72b941d0bd85ba9a8697ec2f |
| institution | Kabale University |
| issn | 2211-3835 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj-art-3ed3067b72b941d0bd85ba9a8697ec2f2025-08-20T05:06:36ZengElsevierActa Pharmaceutica Sinica B2211-38352025-08-011583978399610.1016/j.apsb.2025.06.008FtsZ as a novel target for antibiotics development: Promises and challengesMing-Wei Wang0Kaini Hang1Wei Han2Xin Li3Qingtong Zhou4Dehua Yang5Research Center for Deepsea Bioresources, Sanya 572025, China; Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Corresponding author.Research Center for Deepsea Bioresources, Sanya 572025, China; Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, ChinaResearch Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaResearch Center for Deepsea Bioresources, Sanya 572025, ChinaResearch Center for Deepsea Bioresources, Sanya 572025, China; Research Center for Medicinal Structural Biology, National Research Center for Translational Medicine at Shanghai, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaResearch Center for Deepsea Bioresources, Sanya 572025, China; State Key Laboratory of Chemical Biology and The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, ChinaFilamenting temperature-sensitive mutant Z (FtsZ), a protein essential for bacterial cell division, is highly conserved across bacterial species but absent in humans, positioning it as a strategic target for the development of antibiotics. Significant efforts to identify FtsZ inhibitors—via biochemical assays (e.g., GTPase activity) and cellular approaches (e.g., immunofluorescence)—have yielded over 100 natural products and synthetic compounds, whose cheminformatics clustering underscores a limited chemical diversity among the current scaffolds. Structural studies, including X-ray crystallography and cryo-electron microscopy, have resolved 97 FtsZ structures revealing conserved polymerization mechanisms and conformational plasticity, as exemplified by extremophile adaptations (e.g., Shewanella benthica from the high-pressure environment of the Mariana Trench's Challenger Deep). However, clinical translation is hindered by weak binding affinities, inhibitory inefficacy, dynamic conformational flexibility, and evolving drug resistance linked to FtsZ's functional plasticity. To address these challenges, future efforts should be directed to resolve transient assembly intermediates, leveraging machine learning with high-throughput screening, and integrating structural biology with pharmacokinetic optimization. Multidisciplinary strategies combining these approaches hold promise for translating FtsZ-focused research into clinically viable therapies, addressing the critical unmet need posed by antibiotics resistance.http://www.sciencedirect.com/science/article/pii/S2211383525004113FtsZCell divisionDrug targetCryo-electron microscopyDeepsea bacteriumAntibiotics |
| spellingShingle | Ming-Wei Wang Kaini Hang Wei Han Xin Li Qingtong Zhou Dehua Yang FtsZ as a novel target for antibiotics development: Promises and challenges Acta Pharmaceutica Sinica B FtsZ Cell division Drug target Cryo-electron microscopy Deepsea bacterium Antibiotics |
| title | FtsZ as a novel target for antibiotics development: Promises and challenges |
| title_full | FtsZ as a novel target for antibiotics development: Promises and challenges |
| title_fullStr | FtsZ as a novel target for antibiotics development: Promises and challenges |
| title_full_unstemmed | FtsZ as a novel target for antibiotics development: Promises and challenges |
| title_short | FtsZ as a novel target for antibiotics development: Promises and challenges |
| title_sort | ftsz as a novel target for antibiotics development promises and challenges |
| topic | FtsZ Cell division Drug target Cryo-electron microscopy Deepsea bacterium Antibiotics |
| url | http://www.sciencedirect.com/science/article/pii/S2211383525004113 |
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