Mechanisms of Linezolid Resistance in Mycobacteria
Mycobacteria form some of the most notorious and difficult-to-treat bacterial pathogens. As a group, they are intrinsically resistant to many commonly used antibiotics, such as tetracyclines and beta-lactams. In addition to intrinsic resistances, acquired multidrug resistance has also been observed...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/6/784 |
| _version_ | 1797593115113029632 |
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| author | Wei Chong Gan Hien Fuh Ng Yun Fong Ngeow |
| author_facet | Wei Chong Gan Hien Fuh Ng Yun Fong Ngeow |
| author_sort | Wei Chong Gan |
| collection | DOAJ |
| description | Mycobacteria form some of the most notorious and difficult-to-treat bacterial pathogens. As a group, they are intrinsically resistant to many commonly used antibiotics, such as tetracyclines and beta-lactams. In addition to intrinsic resistances, acquired multidrug resistance has also been observed and documented in <i>Mycobacterium tuberculosis</i> (MTB)<i>, Mycobacterium leprae</i> and non-tuberculous mycobacteria (NTM). To combat multidrug resistant infections by these pathogens, innovative antimicrobials and treatment regimens are required. In this regard, linezolid, an oxazolidinone introduced for clinical use just two decades ago, was added to the therapeutic armamentarium for drug-resistant mycobacteria. It exhibits antibacterial activity by binding to the 50S ribosomal subunit and inhibiting protein synthesis. Unfortunately, linezolid resistance has now been documented in MTB and NTM, in many parts of the world. Most linezolid-resistant mycobacterial strains show mutations in the ribosome or related genes, such as in the <i>rplC, rrl</i> and <i>tsnR</i> genes. Non-ribosomal mechanisms appear to be rare. One such mechanism was associated with a mutation in <i>fadD32</i>, which encodes a protein that plays an important role in mycolic acid synthesis. Mycobacterial efflux proteins have also been implicated in linezolid resistance. This review summarises current knowledge of genetic determinants of linezolid resistance in mycobacteria, with the aim of contributing information that could facilitate the discovery of new therapeutic approaches to overcome, delay or avoid further developments of drug resistance among these important pathogens. |
| first_indexed | 2024-03-11T02:03:15Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T02:03:15Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-754999ca56f24b1597f406f91b68a0832023-11-18T12:01:27ZengMDPI AGPharmaceuticals1424-82472023-05-0116678410.3390/ph16060784Mechanisms of Linezolid Resistance in MycobacteriaWei Chong Gan0Hien Fuh Ng1Yun Fong Ngeow2Dr. Wu Lien-Teh Centre for Research in Communicable Diseases, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Jalan Sungai Long, Bandar Sungai Long, Kajang 43000, Selangor, MalaysiaDr. Wu Lien-Teh Centre for Research in Communicable Diseases, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Jalan Sungai Long, Bandar Sungai Long, Kajang 43000, Selangor, MalaysiaDr. Wu Lien-Teh Centre for Research in Communicable Diseases, M. Kandiah Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Jalan Sungai Long, Bandar Sungai Long, Kajang 43000, Selangor, MalaysiaMycobacteria form some of the most notorious and difficult-to-treat bacterial pathogens. As a group, they are intrinsically resistant to many commonly used antibiotics, such as tetracyclines and beta-lactams. In addition to intrinsic resistances, acquired multidrug resistance has also been observed and documented in <i>Mycobacterium tuberculosis</i> (MTB)<i>, Mycobacterium leprae</i> and non-tuberculous mycobacteria (NTM). To combat multidrug resistant infections by these pathogens, innovative antimicrobials and treatment regimens are required. In this regard, linezolid, an oxazolidinone introduced for clinical use just two decades ago, was added to the therapeutic armamentarium for drug-resistant mycobacteria. It exhibits antibacterial activity by binding to the 50S ribosomal subunit and inhibiting protein synthesis. Unfortunately, linezolid resistance has now been documented in MTB and NTM, in many parts of the world. Most linezolid-resistant mycobacterial strains show mutations in the ribosome or related genes, such as in the <i>rplC, rrl</i> and <i>tsnR</i> genes. Non-ribosomal mechanisms appear to be rare. One such mechanism was associated with a mutation in <i>fadD32</i>, which encodes a protein that plays an important role in mycolic acid synthesis. Mycobacterial efflux proteins have also been implicated in linezolid resistance. This review summarises current knowledge of genetic determinants of linezolid resistance in mycobacteria, with the aim of contributing information that could facilitate the discovery of new therapeutic approaches to overcome, delay or avoid further developments of drug resistance among these important pathogens.https://www.mdpi.com/1424-8247/16/6/784<i>Mycobacterium tuberculosis</i>non-tuberculous mycobacteria<i>Mycobacteroides abscessus</i>linezolid resistancegenetic determinants |
| spellingShingle | Wei Chong Gan Hien Fuh Ng Yun Fong Ngeow Mechanisms of Linezolid Resistance in Mycobacteria Pharmaceuticals <i>Mycobacterium tuberculosis</i> non-tuberculous mycobacteria <i>Mycobacteroides abscessus</i> linezolid resistance genetic determinants |
| title | Mechanisms of Linezolid Resistance in Mycobacteria |
| title_full | Mechanisms of Linezolid Resistance in Mycobacteria |
| title_fullStr | Mechanisms of Linezolid Resistance in Mycobacteria |
| title_full_unstemmed | Mechanisms of Linezolid Resistance in Mycobacteria |
| title_short | Mechanisms of Linezolid Resistance in Mycobacteria |
| title_sort | mechanisms of linezolid resistance in mycobacteria |
| topic | <i>Mycobacterium tuberculosis</i> non-tuberculous mycobacteria <i>Mycobacteroides abscessus</i> linezolid resistance genetic determinants |
| url | https://www.mdpi.com/1424-8247/16/6/784 |
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