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BMC Infectious Diseases
Published in: BMC Infectious Diseases 1/2015

Open Access 01-12-2015 | Research article

Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates

Authors: Zhe Zhang, Jie Yan, Kaijin Xu, Zhongkang Ji, Lanjuan Li

Published in: BMC Infectious Diseases | Issue 1/2015

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Abstract

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.
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Metadata
Title
Tetrandrine reverses drug resistance in isoniazid and ethambutol dual drug-resistant Mycobacterium tuberculosis clinical isolates
Authors
Zhe Zhang
Jie Yan
Kaijin Xu
Zhongkang Ji
Lanjuan Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2015
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-015-0905-0

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