Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis
Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respir...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2022.980844/full |
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| author | Matthew B. McNeil Matthew B. McNeil Chen-Yi Cheung Natalie J. E. Waller Cara Adolph Cassandra L. Chapman Noon E. J. Seeto William Jowsey Zhengqiu Li H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Gregory M. Cook Gregory M. Cook |
| author_facet | Matthew B. McNeil Matthew B. McNeil Chen-Yi Cheung Natalie J. E. Waller Cara Adolph Cassandra L. Chapman Noon E. J. Seeto William Jowsey Zhengqiu Li H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Gregory M. Cook Gregory M. Cook |
| author_sort | Matthew B. McNeil |
| collection | DOAJ |
| description | Mycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respiratory inhibitors have been shown to have synergistic or synthetic lethal interactions, suggesting that combinations of bioenergetic inhibitors could drastically shorten treatment times. Realizing the full potential of this unique target space requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest interactions and potential in a clinical setting. In this review, we discuss (i) chemical-interaction, (ii) genetic-interaction and (iii) chemical-genetic interaction studies to explore the consequences of inhibiting multiple mycobacterial respiratory components. We provide potential mechanisms to describe the basis for the strongest interactions. Finally, whilst we place an emphasis on interactions that occur with existing bioenergetic inhibitors, by highlighting interactions that occur with alternative respiratory components we envision that this information will provide a rational to further explore alternative proteins as potential drug targets and as part of unique drug combinations. |
| first_indexed | 2024-12-10T18:26:14Z |
| format | Article |
| id | doaj.art-ee0242a3a0bb4732ac464a6c58aeb610 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-10T18:26:14Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-ee0242a3a0bb4732ac464a6c58aeb6102022-12-22T01:38:04ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882022-08-011210.3389/fcimb.2022.980844980844Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosisMatthew B. McNeil0Matthew B. McNeil1Chen-Yi Cheung2Natalie J. E. Waller3Cara Adolph4Cassandra L. Chapman5Noon E. J. Seeto6William Jowsey7Zhengqiu Li8H. M. Adnan Hameed9H. M. Adnan Hameed10H. M. Adnan Hameed11H. M. Adnan Hameed12Tianyu Zhang13Tianyu Zhang14Tianyu Zhang15Tianyu Zhang16Gregory M. Cook17Gregory M. Cook18Department of Microbiology and Immunology, University of Otago, Dunedin, New ZealandMaurice Wilkins, Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandSchool of Pharmacy, Jinan University, Guangzhou, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaGuangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases, Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaState Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaChina-New Zealand Joint Laboratory of Biomedicine and Health, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, ChinaGuangdong-Hong Kong-Macau Joint Laboratory of Respiratory Infectious Diseases, Guangzhou, ChinaUniversity of Chinese Academy of Sciences (UCAS), Beijing, ChinaDepartment of Microbiology and Immunology, University of Otago, Dunedin, New ZealandMaurice Wilkins, Centre for Molecular Biodiscovery, The University of Auckland, Auckland, New ZealandMycobacterium tuberculosis remains a leading cause of infectious disease morbidity and mortality for which new drug combination therapies are needed. Mycobacterial bioenergetics has emerged as a promising space for the development of novel therapeutics. Further to this, unique combinations of respiratory inhibitors have been shown to have synergistic or synthetic lethal interactions, suggesting that combinations of bioenergetic inhibitors could drastically shorten treatment times. Realizing the full potential of this unique target space requires an understanding of which combinations of respiratory complexes, when inhibited, have the strongest interactions and potential in a clinical setting. In this review, we discuss (i) chemical-interaction, (ii) genetic-interaction and (iii) chemical-genetic interaction studies to explore the consequences of inhibiting multiple mycobacterial respiratory components. We provide potential mechanisms to describe the basis for the strongest interactions. Finally, whilst we place an emphasis on interactions that occur with existing bioenergetic inhibitors, by highlighting interactions that occur with alternative respiratory components we envision that this information will provide a rational to further explore alternative proteins as potential drug targets and as part of unique drug combinations.https://www.frontiersin.org/articles/10.3389/fcimb.2022.980844/fullrespirationsynthetic lethalitydrug combinationsantibioticssynergy |
| spellingShingle | Matthew B. McNeil Matthew B. McNeil Chen-Yi Cheung Natalie J. E. Waller Cara Adolph Cassandra L. Chapman Noon E. J. Seeto William Jowsey Zhengqiu Li H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed H. M. Adnan Hameed Tianyu Zhang Tianyu Zhang Tianyu Zhang Tianyu Zhang Gregory M. Cook Gregory M. Cook Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis Frontiers in Cellular and Infection Microbiology respiration synthetic lethality drug combinations antibiotics synergy |
| title | Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis |
| title_full | Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis |
| title_fullStr | Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis |
| title_full_unstemmed | Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis |
| title_short | Uncovering interactions between mycobacterial respiratory complexes to target drug-resistant Mycobacterium tuberculosis |
| title_sort | uncovering interactions between mycobacterial respiratory complexes to target drug resistant mycobacterium tuberculosis |
| topic | respiration synthetic lethality drug combinations antibiotics synergy |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2022.980844/full |
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