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Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates
BACKGROUND: Tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Myc...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417324/ https://www.ncbi.nlm.nih.gov/pubmed/25887373 http://dx.doi.org/10.1186/s12879-015-0905-0 |
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author | Zhang, Zhe Yan, Jie Xu, Kaijin Ji, Zhongkang Li, Lanjuan |
author_facet | Zhang, Zhe Yan, Jie Xu, Kaijin Ji, Zhongkang Li, Lanjuan |
author_sort | Zhang, Zhe |
collection | PubMed |
description | BACKGROUND: Tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Mycobacterium tuberculosis (MTB) has turned resistant via efflux mechanisms. METHODS: We screened 200 MTB clinical isolates using drug sensitivity test to look for those who have turned resistant to the drugs most probably due to efflux mechanisms. We found 29 isoniazid (INH) and ethambutol (EMB) - dual resistant (IEDR) strains. Then we tested if treatment with tetrandrine or verapamil could reverse drug resistance to INH and/or EMB in IEDR isolates. RESULTS: There is a parallel resistance among EMB- and INH-resistant strains in the tested clinical isolates. Among INH-resistant strains, 65% was also EMB-resistant. This suggests an involvement of efflux mechanisms which can lead to dual drug resistance in IEDR clinical isolates. Similar to a synthesized efflux pump inhibitor verapamil, tetrandrine treatment together with INH or EMB brought down the MICs from the clinical level of drug resistance to the sensitive range of both drugs. The effective rate reached 82% among IEDR clinical isolates. CONCLUSIONS: Combinational application of tetrandrine with INH or EMB increased drug efficacy. Drugs like tetrandrine may help to reduce drug dosage thus alleviate side effects. |
format | Online Article Text |
id | pubmed-4417324 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44173242015-05-03 Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates Zhang, Zhe Yan, Jie Xu, Kaijin Ji, Zhongkang Li, Lanjuan BMC Infect Dis Research Article BACKGROUND: Tetrandrine is a natural chemical product purified from fourstamen stephania root which recently has been shown to act similarly as synthesized drug efflux pump inhibitor verapamil. The aim of the study is to examine whether tetrandrine could potentiate anti-tubercular drugs to which Mycobacterium tuberculosis (MTB) has turned resistant via efflux mechanisms. METHODS: We screened 200 MTB clinical isolates using drug sensitivity test to look for those who have turned resistant to the drugs most probably due to efflux mechanisms. We found 29 isoniazid (INH) and ethambutol (EMB) - dual resistant (IEDR) strains. Then we tested if treatment with tetrandrine or verapamil could reverse drug resistance to INH and/or EMB in IEDR isolates. RESULTS: There is a parallel resistance among EMB- and INH-resistant strains in the tested clinical isolates. Among INH-resistant strains, 65% was also EMB-resistant. This suggests an involvement of efflux mechanisms which can lead to dual drug resistance in IEDR clinical isolates. Similar to a synthesized efflux pump inhibitor verapamil, tetrandrine treatment together with INH or EMB brought down the MICs from the clinical level of drug resistance to the sensitive range of both drugs. The effective rate reached 82% among IEDR clinical isolates. CONCLUSIONS: Combinational application of tetrandrine with INH or EMB increased drug efficacy. Drugs like tetrandrine may help to reduce drug dosage thus alleviate side effects. BioMed Central 2015-03-25 /pmc/articles/PMC4417324/ /pubmed/25887373 http://dx.doi.org/10.1186/s12879-015-0905-0 Text en © Zhang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Zhang, Zhe Yan, Jie Xu, Kaijin Ji, Zhongkang Li, Lanjuan Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title | Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title_full | Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title_fullStr | Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title_full_unstemmed | Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title_short | Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates |
title_sort | tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant mycobacterium tuberculosis clinical isolates |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417324/ https://www.ncbi.nlm.nih.gov/pubmed/25887373 http://dx.doi.org/10.1186/s12879-015-0905-0 |
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