Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis
Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these i...
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Frontiers Media S.A.
2024-01-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2023.1304857/full |
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| author | Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Shah Alam Md Shah Alam Md Shah Alam Md Shah Alam Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Buhari Yusuf Buhari Yusuf Buhari Yusuf Buhari Yusuf H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Xirong Tian Xirong Tian Xirong Tian Xirong Tian Chiranjibi Chhotaray Rajesh Basnet Rajesh Basnet Rajesh Basnet Rajesh Basnet Haftay Abraha Haftay Abraha Haftay Abraha Haftay Abraha Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Cuiting Fang Cuiting Fang Cuiting Fang Cuiting Fang Chunyu Li Chunyu Li Chunyu Li Chunyu Li Sohel Hasan Shouyong Tan Shouyong Tan Nanshan Zhong Nanshan Zhong Nanshan Zhong Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang |
| author_facet | Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Shah Alam Md Shah Alam Md Shah Alam Md Shah Alam Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Buhari Yusuf Buhari Yusuf Buhari Yusuf Buhari Yusuf H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Xirong Tian Xirong Tian Xirong Tian Xirong Tian Chiranjibi Chhotaray Rajesh Basnet Rajesh Basnet Rajesh Basnet Rajesh Basnet Haftay Abraha Haftay Abraha Haftay Abraha Haftay Abraha Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Cuiting Fang Cuiting Fang Cuiting Fang Cuiting Fang Chunyu Li Chunyu Li Chunyu Li Chunyu Li Sohel Hasan Shouyong Tan Shouyong Tan Nanshan Zhong Nanshan Zhong Nanshan Zhong Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang |
| author_sort | Md Mahmudul Islam |
| collection | DOAJ |
| description | Clofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) Mtb strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against Mtb strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the Rv0678, pepQ, Rv1979c, and atpE genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against Mtb can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB. |
| first_indexed | 2024-03-08T14:45:54Z |
| format | Article |
| id | doaj.art-53aceef45fd5414d90a3e7b3c19004b3 |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-03-08T14:45:54Z |
| publishDate | 2024-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-53aceef45fd5414d90a3e7b3c19004b32024-01-11T09:50:37ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2024-01-011010.3389/fmed.2023.13048571304857Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosisMd Mahmudul Islam0Md Mahmudul Islam1Md Mahmudul Islam2Md Mahmudul Islam3Md Mahmudul Islam4Md Shah Alam5Md Shah Alam6Md Shah Alam7Md Shah Alam8Zhiyong Liu9Zhiyong Liu10Zhiyong Liu11Zhiyong Liu12Zhiyong Liu13Mst Sumaia Khatun14Mst Sumaia Khatun15Mst Sumaia Khatun16Mst Sumaia Khatun17Buhari Yusuf18Buhari Yusuf19Buhari Yusuf20Buhari Yusuf21H. M. Adnan Hameed22H. M. Adnan Hameed23H. M. Adnan Hameed24H. M. Adnan Hameed25Xirong Tian26Xirong Tian27Xirong Tian28Xirong Tian29Chiranjibi Chhotaray30Rajesh Basnet31Rajesh Basnet32Rajesh Basnet33Rajesh Basnet34Haftay Abraha35Haftay Abraha36Haftay Abraha37Haftay Abraha38Xiaofan Zhang39Xiaofan Zhang40Xiaofan Zhang41Xiaofan Zhang42Shahzad Akbar Khan43Shahzad Akbar Khan44Shahzad Akbar Khan45Shahzad Akbar Khan46Shahzad Akbar Khan47Cuiting Fang48Cuiting Fang49Cuiting Fang50Cuiting Fang51Chunyu Li52Chunyu Li53Chunyu Li54Chunyu Li55Sohel Hasan56Shouyong Tan57Shouyong Tan58Nanshan Zhong59Nanshan Zhong60Nanshan Zhong61Jinxing Hu62Jinxing Hu63Tianyu Zhang64Tianyu Zhang65Tianyu Zhang66Tianyu Zhang67State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Microbiology, Shaheed Shamsuzzoha Institute of Biosciences, Affiliated with University of Rajshahi, Rajshahi, BangladeshState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangzhou Medical University, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaDepartment of Medicine, Center for Emerging Pathogens, Rutgers-New Jersey Medical School, Newark, NJ, United StatesState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaLaboratory of Pathology, Department of Pathobiology, University of Poonch Rawalakot, Azad Kashmir, PakistanState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China0Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, BangladeshGuangzhou National Laboratory, Guangzhou, China1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, China2State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The National Center for Respiratory Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, ChinaGuangzhou National Laboratory, Guangzhou, China1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaChina-New Zealand Joint Laboratory on Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaClofazimine (CFZ) and bedaquiline (BDQ) are currently used for the treatment of multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) strains. In recent years, adding CFZ and BDQ to tuberculosis (TB) drug regimens against MDR Mtb strains has significantly improved treatment results, but these improvements are threatened by the emergence of MDR and extensively drug-resistant (XDR) Mtb strains. Recently, CFZ and BDQ have attracted much attention for their strong clinical efficacy, although very little is known about the mechanisms of action, drug susceptibility test (DST), resistance mechanisms, cross-resistance, and pharmacokinetics of these two drugs. In this current review, we provide recent updates on the mechanisms of action, DST, associated mutations with individual resistance and cross-resistance, clinical efficacy, and pharmacokinetics of CFZ and BDQ against Mtb strains. Presently, known mechanisms of resistance for CFZ and/or BDQ include mutations within the Rv0678, pepQ, Rv1979c, and atpE genes. The cross-resistance between CFZ and BDQ may reduce available MDR-/XDR-TB treatment options. The use of CFZ and BDQ for treatment in the setting of limited DST could allow further spread of drug resistance. The DST and resistance knowledge are urgently needed where CFZ and BDQ resistance do emerge. Therefore, an in-depth understanding of clinical efficacy, DST, cross-resistance, and pharmacokinetics for CFZ and BDQ against Mtb can provide new ideas for improving treatment outcomes, reducing mortality, preventing drug resistance, and TB transmission. Along with this, it will also help to develop rapid molecular diagnostic tools as well as novel therapeutic drugs for TB.https://www.frontiersin.org/articles/10.3389/fmed.2023.1304857/fullcross-resistancedrug resistancemechanism of actionmolecular diagnosticregimenstreatment |
| spellingShingle | Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Mahmudul Islam Md Shah Alam Md Shah Alam Md Shah Alam Md Shah Alam Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Zhiyong Liu Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Mst Sumaia Khatun Buhari Yusuf Buhari Yusuf Buhari Yusuf Buhari Yusuf H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Xirong Tian Xirong Tian Xirong Tian Xirong Tian Chiranjibi Chhotaray Rajesh Basnet Rajesh Basnet Rajesh Basnet Rajesh Basnet Haftay Abraha Haftay Abraha Haftay Abraha Haftay Abraha Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Xiaofan Zhang Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Shahzad Akbar Khan Cuiting Fang Cuiting Fang Cuiting Fang Cuiting Fang Chunyu Li Chunyu Li Chunyu Li Chunyu Li Sohel Hasan Shouyong Tan Shouyong Tan Nanshan Zhong Nanshan Zhong Nanshan Zhong Jinxing Hu Jinxing Hu Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis Frontiers in Medicine cross-resistance drug resistance mechanism of action molecular diagnostic regimens treatment |
| title | Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis |
| title_full | Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis |
| title_fullStr | Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis |
| title_full_unstemmed | Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis |
| title_short | Molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against Mycobacterium tuberculosis |
| title_sort | molecular mechanisms of resistance and treatment efficacy of clofazimine and bedaquiline against mycobacterium tuberculosis |
| topic | cross-resistance drug resistance mechanism of action molecular diagnostic regimens treatment |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2023.1304857/full |
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