Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity
Staphylococcus aureus (S. aureus) is a prevalent pathogen responsible for a wide range of diseases in humans, contributing to both hospital-acquired and community-acquired infections. The von Willebrand factor-binding protein (vWbp) is pivotal for S. aureus pathogenicity because it induces blood coa...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Virulence |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/21505594.2024.2445799 |
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| author | Shiyu Zhou Haoyan Zou Yueshan Xu Dongbin Guo Zhengjie Su Li Wang Bingmei Wang Yicheng Zhao Xiangyang Leng Yanping Wang |
| author_facet | Shiyu Zhou Haoyan Zou Yueshan Xu Dongbin Guo Zhengjie Su Li Wang Bingmei Wang Yicheng Zhao Xiangyang Leng Yanping Wang |
| author_sort | Shiyu Zhou |
| collection | DOAJ |
| description | Staphylococcus aureus (S. aureus) is a prevalent pathogen responsible for a wide range of diseases in humans, contributing to both hospital-acquired and community-acquired infections. The von Willebrand factor-binding protein (vWbp) is pivotal for S. aureus pathogenicity because it induces blood coagulation, thereby facilitating bacterial survival and dissemination within the host. Notably, the absence of vWbp does not hinder S. aureus growth, indicating that vWbp is an attractive target for combating S. aureus infections while mitigating the risk of antibiotic resistance. Our findings revealed that tanshinone I significantly inhibited vWbp-induced coagulation without affecting the proliferation of S. aureus. Hemolysis assays confirmed the biocompatibility of tanshinone I, while Western blot analysis, fluorescence quenching, and thermal shift assays (TSAs) demonstrated that tanshinone I does not alter vWbp expression but directly binds to the protein. Molecular docking studies elucidated the interaction mechanism, identifying ARG-479 and GLN-484 as critical residues for tanshinone I binding. Furthermore, in vivo studies demonstrated that tanshinone I reduces lung tissue damage in mice infected with S. aureus, thereby increasing survival rates. Additionally, tanshinone I was tested in greater wax moth larvae and showed similar protective effects. In conclusion, tanshinone I effectively inhibits vWbp, reducing the virulence of S. aureus. This study underscores the potential of tanshinone I as a therapeutic agent against S. aureus infections, offering a novel strategy to combat bacterial infections while decreasing the critical issue of antibiotic resistance. |
| format | Article |
| id | doaj-art-e0caba3efc8f4210b61e937d11e41b9f |
| institution | Kabale University |
| issn | 2150-5594 2150-5608 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Virulence |
| spelling | doaj-art-e0caba3efc8f4210b61e937d11e41b9f2024-12-30T20:40:36ZengTaylor & Francis GroupVirulence2150-55942150-56082025-12-0116110.1080/21505594.2024.2445799Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicityShiyu Zhou0Haoyan Zou1Yueshan Xu2Dongbin Guo3Zhengjie Su4Li Wang5Bingmei Wang6Yicheng Zhao7Xiangyang Leng8Yanping Wang9College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, ChinaCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, ChinaCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaClinical Medical College, Changchun University of Chinese Medicine, Changchun, ChinaClinical Medical College, Changchun University of Chinese Medicine, Changchun, ChinaChinese Medicine Guangdong Laboratory, Hengqin, Guangdong, ChinaCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, ChinaObstetrics and Gynecology Diagnosis and Treatment Center, Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, ChinaStaphylococcus aureus (S. aureus) is a prevalent pathogen responsible for a wide range of diseases in humans, contributing to both hospital-acquired and community-acquired infections. The von Willebrand factor-binding protein (vWbp) is pivotal for S. aureus pathogenicity because it induces blood coagulation, thereby facilitating bacterial survival and dissemination within the host. Notably, the absence of vWbp does not hinder S. aureus growth, indicating that vWbp is an attractive target for combating S. aureus infections while mitigating the risk of antibiotic resistance. Our findings revealed that tanshinone I significantly inhibited vWbp-induced coagulation without affecting the proliferation of S. aureus. Hemolysis assays confirmed the biocompatibility of tanshinone I, while Western blot analysis, fluorescence quenching, and thermal shift assays (TSAs) demonstrated that tanshinone I does not alter vWbp expression but directly binds to the protein. Molecular docking studies elucidated the interaction mechanism, identifying ARG-479 and GLN-484 as critical residues for tanshinone I binding. Furthermore, in vivo studies demonstrated that tanshinone I reduces lung tissue damage in mice infected with S. aureus, thereby increasing survival rates. Additionally, tanshinone I was tested in greater wax moth larvae and showed similar protective effects. In conclusion, tanshinone I effectively inhibits vWbp, reducing the virulence of S. aureus. This study underscores the potential of tanshinone I as a therapeutic agent against S. aureus infections, offering a novel strategy to combat bacterial infections while decreasing the critical issue of antibiotic resistance.https://www.tandfonline.com/doi/10.1080/21505594.2024.2445799von Willebrandfactor-binding proteintanshinone IS. aureusvirulence |
| spellingShingle | Shiyu Zhou Haoyan Zou Yueshan Xu Dongbin Guo Zhengjie Su Li Wang Bingmei Wang Yicheng Zhao Xiangyang Leng Yanping Wang Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity Virulence von Willebrandfactor-binding protein tanshinone I S. aureus virulence |
| title | Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity |
| title_full | Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity |
| title_fullStr | Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity |
| title_full_unstemmed | Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity |
| title_short | Tanshinone I as a novel therapeutic agent targeting von Willebrand factor-binding protein to mitigate Staphylococcus aureus pathogenicity |
| title_sort | tanshinone i as a novel therapeutic agent targeting von willebrand factor binding protein to mitigate staphylococcus aureus pathogenicity |
| topic | von Willebrandfactor-binding protein tanshinone I S. aureus virulence |
| url | https://www.tandfonline.com/doi/10.1080/21505594.2024.2445799 |
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