How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance
Ethionamide (ETH) is a second-line antituberculosis drug. ETH resistance (ETH-R) is mainly related to the mutations of the monooxygenase-activating ETH (EthA), the ETH target (InhA), and the <i>inhA</i> promoter. Nonetheless, diagnosing ETH-R is still challenging. We assessed the strateg...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/7/1436 |
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| author | Thomas Maitre Florence Morel Florence Brossier Wladimir Sougakoff Jéremy Jaffre Sokleaph Cheng Nicolas Veziris Alexandra Aubry on behalf of the NRC-MyRMA |
| author_facet | Thomas Maitre Florence Morel Florence Brossier Wladimir Sougakoff Jéremy Jaffre Sokleaph Cheng Nicolas Veziris Alexandra Aubry on behalf of the NRC-MyRMA |
| author_sort | Thomas Maitre |
| collection | DOAJ |
| description | Ethionamide (ETH) is a second-line antituberculosis drug. ETH resistance (ETH-R) is mainly related to the mutations of the monooxygenase-activating ETH (EthA), the ETH target (InhA), and the <i>inhA</i> promoter. Nonetheless, diagnosing ETH-R is still challenging. We assessed the strategy used for detecting ETH-R at the French National Reference Center for Mycobacteria in 497 MDR-TB isolates received from 2008 to 2016. The genotypic ETH’s resistance detection was performed by sequencing <i>ethA</i>, <i>ethR</i>, the <i>ethA-ethR</i> intergenic region, and the <i>inhA</i> promoter in the 497 multidrug-resistant isolates, whereas the phenotypic ETH susceptibility testing (PST) was performed using the reference proportion method. Mutations were found in up to 76% of the 387 resistant isolates and in up to 28% of the 110 susceptible isolates. Our results do not support the role of <i>ethR</i> mutations in ETH resistance. Altogether, the positive predictive value of our genotypic strategy to diagnose ETH-R was improved when only considering the variants included in the WHO catalogue and in other databases, such as TB-Profiler. Therefore, our work will help to update the list of mutations that could be graded as being associated with resistance to improve ETH-R diagnosis. |
| first_indexed | 2024-03-09T10:14:36Z |
| format | Article |
| id | doaj.art-a1cae6dc041442dc9a9d0b5a2598a7be |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T10:14:36Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-a1cae6dc041442dc9a9d0b5a2598a7be2023-12-01T22:28:39ZengMDPI AGMicroorganisms2076-26072022-07-01107143610.3390/microorganisms10071436How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide ResistanceThomas Maitre0Florence Morel1Florence Brossier2Wladimir Sougakoff3Jéremy Jaffre4Sokleaph Cheng5Nicolas Veziris6Alexandra Aubry7on behalf of the NRC-MyRMACentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceCentre National de Référence des Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Hôpital Pitié-Salpêtrière, AP-HP (Assistance Publique Hôpitaux de Paris), Sorbonne-Université, F-75013 Paris, FranceEthionamide (ETH) is a second-line antituberculosis drug. ETH resistance (ETH-R) is mainly related to the mutations of the monooxygenase-activating ETH (EthA), the ETH target (InhA), and the <i>inhA</i> promoter. Nonetheless, diagnosing ETH-R is still challenging. We assessed the strategy used for detecting ETH-R at the French National Reference Center for Mycobacteria in 497 MDR-TB isolates received from 2008 to 2016. The genotypic ETH’s resistance detection was performed by sequencing <i>ethA</i>, <i>ethR</i>, the <i>ethA-ethR</i> intergenic region, and the <i>inhA</i> promoter in the 497 multidrug-resistant isolates, whereas the phenotypic ETH susceptibility testing (PST) was performed using the reference proportion method. Mutations were found in up to 76% of the 387 resistant isolates and in up to 28% of the 110 susceptible isolates. Our results do not support the role of <i>ethR</i> mutations in ETH resistance. Altogether, the positive predictive value of our genotypic strategy to diagnose ETH-R was improved when only considering the variants included in the WHO catalogue and in other databases, such as TB-Profiler. Therefore, our work will help to update the list of mutations that could be graded as being associated with resistance to improve ETH-R diagnosis.https://www.mdpi.com/2076-2607/10/7/1436ethionamidetuberculosisresistancemolecular diagnosis |
| spellingShingle | Thomas Maitre Florence Morel Florence Brossier Wladimir Sougakoff Jéremy Jaffre Sokleaph Cheng Nicolas Veziris Alexandra Aubry on behalf of the NRC-MyRMA How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance Microorganisms ethionamide tuberculosis resistance molecular diagnosis |
| title | How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance |
| title_full | How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance |
| title_fullStr | How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance |
| title_full_unstemmed | How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance |
| title_short | How a PCR Sequencing Strategy Can Bring New Data to Improve the Diagnosis of Ethionamide Resistance |
| title_sort | how a pcr sequencing strategy can bring new data to improve the diagnosis of ethionamide resistance |
| topic | ethionamide tuberculosis resistance molecular diagnosis |
| url | https://www.mdpi.com/2076-2607/10/7/1436 |
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