Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics
Abstract Global multidrug‐resistant (MDR) bacteria are spreading rapidly and causing a great threat to human health due to the abuse of antibiotics. Determining how to resensitize MDR bacteria to conventional inefficient antibiotics is of extreme urgency. Here, a low‐temperature photothermal treatme...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-05-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.201902070 |
| _version_ | 1818447293269934080 |
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| author | Lei Tan Ziao Zhou Xiangmei Liu Jun Li Yufeng Zheng Zhenduo Cui Xianjin Yang Yanqin Liang Zhaoyang Li Xiaobo Feng Shengli Zhu Kelvin Wai Kwok Yeung Cao Yang Xianbao Wang Shuilin Wu |
| author_facet | Lei Tan Ziao Zhou Xiangmei Liu Jun Li Yufeng Zheng Zhenduo Cui Xianjin Yang Yanqin Liang Zhaoyang Li Xiaobo Feng Shengli Zhu Kelvin Wai Kwok Yeung Cao Yang Xianbao Wang Shuilin Wu |
| author_sort | Lei Tan |
| collection | DOAJ |
| description | Abstract Global multidrug‐resistant (MDR) bacteria are spreading rapidly and causing a great threat to human health due to the abuse of antibiotics. Determining how to resensitize MDR bacteria to conventional inefficient antibiotics is of extreme urgency. Here, a low‐temperature photothermal treatment (PTT, 45 °C) is utilized with red phosphorus nanoparticles to resensitize methicillin‐resistant Staphylococcus aureus (MRSA) to conventional aminoglycoside antibiotics. The antibacterial mechanism is studied by the proteomic technique and molecular dynamics (MD) simulation, which proves that the aminoglycoside antibiotics against MRSA can be selectively potentiated by low‐temperature PTT. The catalytic activity of 2‐aminoglycoside phosphotransferase (APH (2″))—a modifying enzyme—is demonstrated to be obviously inhibited via detecting the consumption of adenosine triphosphate (ATP) in the catalytic reaction. It is also found that the active site of aspartic acid (ASP) residues in APH (2″) is thermally unstable from the results of molecular dynamics simulation. Its catalytic ability is inhibited by preventing the deprotonating procedure for the target OH of gentamycin. The combined therapy also exhibits great biocompatibility and successfully treats MRSA infections in vivo. This low‐temperature PTT strategy has the potential to be an exogenous‐modifying enzyme inhibitor for the treatment of MDR bacterial infection. |
| first_indexed | 2024-12-14T20:01:19Z |
| format | Article |
| id | doaj.art-14e45a22a7cf4f20b04256eb086ef193 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-14T20:01:19Z |
| publishDate | 2020-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-14e45a22a7cf4f20b04256eb086ef1932022-12-21T22:49:08ZengWileyAdvanced Science2198-38442020-05-0179n/an/a10.1002/advs.201902070Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside AntibioticsLei Tan0Ziao Zhou1Xiangmei Liu2Jun Li3Yufeng Zheng4Zhenduo Cui5Xianjin Yang6Yanqin Liang7Zhaoyang Li8Xiaobo Feng9Shengli Zhu10Kelvin Wai Kwok Yeung11Cao Yang12Xianbao Wang13Shuilin Wu14Hubei Key Laboratory of Polymer Materials Ministry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science & Engineering Hubei University Wuhan 430062 ChinaHubei Key Laboratory of Polymer Materials Ministry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science & Engineering Hubei University Wuhan 430062 ChinaHubei Key Laboratory of Polymer Materials Ministry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science & Engineering Hubei University Wuhan 430062 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaState Key Laboratory for Turbulence and Complex System and Department of Materials Science and Engineering College of Engineering Peking University Beijing 100871 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaDepartment of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaSchool of Materials Science & Engineering The Key Laboratory of Advanced Ceramics and Machining Technology by the Ministry of Education of China Tianjin University Tianjin 300072 ChinaDepartment of Orthopaedics & Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong ChinaDepartment of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaHubei Key Laboratory of Polymer Materials Ministry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science & Engineering Hubei University Wuhan 430062 ChinaHubei Key Laboratory of Polymer Materials Ministry‐of‐Education Key Laboratory for the Green Preparation and Application of Functional Materials School of Materials Science & Engineering Hubei University Wuhan 430062 ChinaAbstract Global multidrug‐resistant (MDR) bacteria are spreading rapidly and causing a great threat to human health due to the abuse of antibiotics. Determining how to resensitize MDR bacteria to conventional inefficient antibiotics is of extreme urgency. Here, a low‐temperature photothermal treatment (PTT, 45 °C) is utilized with red phosphorus nanoparticles to resensitize methicillin‐resistant Staphylococcus aureus (MRSA) to conventional aminoglycoside antibiotics. The antibacterial mechanism is studied by the proteomic technique and molecular dynamics (MD) simulation, which proves that the aminoglycoside antibiotics against MRSA can be selectively potentiated by low‐temperature PTT. The catalytic activity of 2‐aminoglycoside phosphotransferase (APH (2″))—a modifying enzyme—is demonstrated to be obviously inhibited via detecting the consumption of adenosine triphosphate (ATP) in the catalytic reaction. It is also found that the active site of aspartic acid (ASP) residues in APH (2″) is thermally unstable from the results of molecular dynamics simulation. Its catalytic ability is inhibited by preventing the deprotonating procedure for the target OH of gentamycin. The combined therapy also exhibits great biocompatibility and successfully treats MRSA infections in vivo. This low‐temperature PTT strategy has the potential to be an exogenous‐modifying enzyme inhibitor for the treatment of MDR bacterial infection.https://doi.org/10.1002/advs.201902070aminoglycoside antibioticsantibacterial effectMRSAphotothermal treatmentred phosphorus nanoparticles |
| spellingShingle | Lei Tan Ziao Zhou Xiangmei Liu Jun Li Yufeng Zheng Zhenduo Cui Xianjin Yang Yanqin Liang Zhaoyang Li Xiaobo Feng Shengli Zhu Kelvin Wai Kwok Yeung Cao Yang Xianbao Wang Shuilin Wu Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics Advanced Science aminoglycoside antibiotics antibacterial effect MRSA photothermal treatment red phosphorus nanoparticles |
| title | Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics |
| title_full | Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics |
| title_fullStr | Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics |
| title_full_unstemmed | Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics |
| title_short | Overcoming Multidrug‐Resistant MRSA Using Conventional Aminoglycoside Antibiotics |
| title_sort | overcoming multidrug resistant mrsa using conventional aminoglycoside antibiotics |
| topic | aminoglycoside antibiotics antibacterial effect MRSA photothermal treatment red phosphorus nanoparticles |
| url | https://doi.org/10.1002/advs.201902070 |
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