Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i>
<i>Mycobacteroides abscessus</i> (formerly <i>Mycobacterium abscessus</i>) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of <i>M. abscessus</i> towards firs...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/11/5/572 |
| _version_ | 1797502150222282752 |
|---|---|
| author | Hien Fuh Ng Yun Fong Ngeow |
| author_facet | Hien Fuh Ng Yun Fong Ngeow |
| author_sort | Hien Fuh Ng |
| collection | DOAJ |
| description | <i>Mycobacteroides abscessus</i> (formerly <i>Mycobacterium abscessus</i>) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of <i>M. abscessus</i> towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX (<i>MAB_1496c</i>). Tigecycline, a third-generation tetracycline, is a poor substrate for the MabTetX and does not induce the expression of this enzyme. Although tigecycline-resistant strains of <i>M. abscessus</i> have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in <i>M. abscessus</i> revealed the involvement of the gene <i>MAB_3508c</i> which encodes the transcriptional activator WhiB7, as well as mutations in the <i>sigH-rshA</i> genes which control heat shock and oxidative-stress responses. The deletion of <i>whiB7</i> has been observed to cause a 4-fold decrease in the minimum inhibitory concentration of tigecycline. In the absence of environmental stress, the SigH sigma factor (<i>MAB_3543c</i>) interacts with and is inhibited by the anti-sigma factor RshA (<i>MAB_3542c</i>). The disruption of the SigH-RshA interaction resulting from mutations and the subsequent up-regulation of SigH have been hypothesized to lead to tigecycline resistance in <i>M. abscessus</i>. In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in <i>M. abscessus</i> was examined and discussed. |
| first_indexed | 2024-03-10T03:28:48Z |
| format | Article |
| id | doaj.art-e791f0e99fe64ebaa07719314d7a020b |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T03:28:48Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-e791f0e99fe64ebaa07719314d7a020b2023-11-23T09:47:57ZengMDPI AGAntibiotics2079-63822022-04-0111557210.3390/antibiotics11050572Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i>Hien Fuh Ng0Yun Fong Ngeow1Centre for Research on Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang 43000, MalaysiaCentre for Research on Communicable Diseases, Faculty of Medicine and Health Sciences, Universiti Tunku Abdul Rahman, Kajang 43000, Malaysia<i>Mycobacteroides abscessus</i> (formerly <i>Mycobacterium abscessus</i>) is a clinically important, rapid-growing non-tuberculous mycobacterium notoriously known for its multidrug-resistance phenotype. The intrinsic resistance of <i>M. abscessus</i> towards first- and second-generation tetracyclines is mainly due to the over-expression of a tetracycline-degrading enzyme known as MabTetX (<i>MAB_1496c</i>). Tigecycline, a third-generation tetracycline, is a poor substrate for the MabTetX and does not induce the expression of this enzyme. Although tigecycline-resistant strains of <i>M. abscessus</i> have been documented in different parts of the world, their resistance determinants remain largely elusive. Recent work on tigecycline resistance or reduced susceptibility in <i>M. abscessus</i> revealed the involvement of the gene <i>MAB_3508c</i> which encodes the transcriptional activator WhiB7, as well as mutations in the <i>sigH-rshA</i> genes which control heat shock and oxidative-stress responses. The deletion of <i>whiB7</i> has been observed to cause a 4-fold decrease in the minimum inhibitory concentration of tigecycline. In the absence of environmental stress, the SigH sigma factor (<i>MAB_3543c</i>) interacts with and is inhibited by the anti-sigma factor RshA (<i>MAB_3542c</i>). The disruption of the SigH-RshA interaction resulting from mutations and the subsequent up-regulation of SigH have been hypothesized to lead to tigecycline resistance in <i>M. abscessus</i>. In this review, the evidence for different genetic determinants reported to be linked to tigecycline resistance in <i>M. abscessus</i> was examined and discussed.https://www.mdpi.com/2079-6382/11/5/572<i>Mycobacteroides abscessus</i>tigecyclineresistancegenetic determinantsWhiB7SigH |
| spellingShingle | Hien Fuh Ng Yun Fong Ngeow Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> Antibiotics <i>Mycobacteroides abscessus</i> tigecycline resistance genetic determinants WhiB7 SigH |
| title | Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> |
| title_full | Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> |
| title_fullStr | Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> |
| title_full_unstemmed | Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> |
| title_short | Genetic Determinants of Tigecycline Resistance in <i>Mycobacteroides abscessus</i> |
| title_sort | genetic determinants of tigecycline resistance in i mycobacteroides abscessus i |
| topic | <i>Mycobacteroides abscessus</i> tigecycline resistance genetic determinants WhiB7 SigH |
| url | https://www.mdpi.com/2079-6382/11/5/572 |
| work_keys_str_mv | AT hienfuhng geneticdeterminantsoftigecyclineresistanceinimycobacteroidesabscessusi AT yunfongngeow geneticdeterminantsoftigecyclineresistanceinimycobacteroidesabscessusi |