Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms
Multidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that nigericin showed potent bactericidal activity aga...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1055929/full |
| _version_ | 1798004278308110336 |
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| author | Xiaoli Zhu Xiaoli Zhu Anjin Hong Anjin Hong Xihuan Sun Weijie Wang Guanghui He Guanghui He Huan Luo Zhenhua Wu Zhenhua Wu Qingyan Xu Qingyan Xu Zhiyu Hu Zhiyu Hu Xiaobing Wu Xiaobing Wu Donghong Huang Li Li Li Li Xilin Zhao Xianming Deng Xianming Deng |
| author_facet | Xiaoli Zhu Xiaoli Zhu Anjin Hong Anjin Hong Xihuan Sun Weijie Wang Guanghui He Guanghui He Huan Luo Zhenhua Wu Zhenhua Wu Qingyan Xu Qingyan Xu Zhiyu Hu Zhiyu Hu Xiaobing Wu Xiaobing Wu Donghong Huang Li Li Li Li Xilin Zhao Xianming Deng Xianming Deng |
| author_sort | Xiaoli Zhu |
| collection | DOAJ |
| description | Multidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that nigericin showed potent bactericidal activity against various clinical MDR Gram-positive bacteria, persisters and biofilms, with low frequencies of resistance development. Moreover, nigericin exhibited favorable in vivo efficacy in deep-seated mouse biofilm, murine skin and bloodstream infection models. With Staphylococcus aureus, nigericin disrupted ATP production and electron transport chain; cell death was associated with altered membrane structure and permeability. Obtaining nigericin-resistant/tolerant mutants required multiple rounds of challenge, and, cross-resistance to members of several antimicrobial classes was absent, probably due to distinct nigericin action with the GraSR two-component regulatory system. Thus, our work reveals that nigericin is a promising antibiotic candidate for the treatment of chronic or recurrent infections caused by Gram-positive bacteria. |
| first_indexed | 2024-04-11T12:22:12Z |
| format | Article |
| id | doaj.art-0c3a4b61daa84b25af22f8e3b6d09184 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-11T12:22:12Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-0c3a4b61daa84b25af22f8e3b6d091842022-12-22T04:24:04ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-12-011210.3389/fcimb.2022.10559291055929Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilmsXiaoli Zhu0Xiaoli Zhu1Anjin Hong2Anjin Hong3Xihuan Sun4Weijie Wang5Guanghui He6Guanghui He7Huan Luo8Zhenhua Wu9Zhenhua Wu10Qingyan Xu11Qingyan Xu12Zhiyu Hu13Zhiyu Hu14Xiaobing Wu15Xiaobing Wu16Donghong Huang17Li Li18Li Li19Xilin Zhao20Xianming Deng21Xianming Deng22State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaClinical Microbiology Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaClinical Microbiology Laboratory, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, Fujian, ChinaState Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, ChinaState-province Joint Engineering Laboratory of Targeted Drugs from Natural Products, Xiamen University, Xiamen, Fujian, ChinaMultidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that nigericin showed potent bactericidal activity against various clinical MDR Gram-positive bacteria, persisters and biofilms, with low frequencies of resistance development. Moreover, nigericin exhibited favorable in vivo efficacy in deep-seated mouse biofilm, murine skin and bloodstream infection models. With Staphylococcus aureus, nigericin disrupted ATP production and electron transport chain; cell death was associated with altered membrane structure and permeability. Obtaining nigericin-resistant/tolerant mutants required multiple rounds of challenge, and, cross-resistance to members of several antimicrobial classes was absent, probably due to distinct nigericin action with the GraSR two-component regulatory system. Thus, our work reveals that nigericin is a promising antibiotic candidate for the treatment of chronic or recurrent infections caused by Gram-positive bacteria.https://www.frontiersin.org/articles/10.3389/fcimb.2022.1055929/fullmultidrug-resistant bacteriapersisterbiofilmMRSAantibioticmechanism of action |
| spellingShingle | Xiaoli Zhu Xiaoli Zhu Anjin Hong Anjin Hong Xihuan Sun Weijie Wang Guanghui He Guanghui He Huan Luo Zhenhua Wu Zhenhua Wu Qingyan Xu Qingyan Xu Zhiyu Hu Zhiyu Hu Xiaobing Wu Xiaobing Wu Donghong Huang Li Li Li Li Xilin Zhao Xianming Deng Xianming Deng Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms Frontiers in Cellular and Infection Microbiology multidrug-resistant bacteria persister biofilm MRSA antibiotic mechanism of action |
| title | Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms |
| title_full | Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms |
| title_fullStr | Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms |
| title_full_unstemmed | Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms |
| title_short | Nigericin is effective against multidrug resistant gram-positive bacteria, persisters, and biofilms |
| title_sort | nigericin is effective against multidrug resistant gram positive bacteria persisters and biofilms |
| topic | multidrug-resistant bacteria persister biofilm MRSA antibiotic mechanism of action |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.1055929/full |
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