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Park, Shin, Kim, Koh, Kwon, Kim, Kook, Cho, Lew, and Bai: Implication of embB Gene Mutation in Ethambutol-Susceptible Clinical Isolates of Mycobacterium tuberculosis
Original Article
In Vitro

Tuberculosis and Respiratory Diseases 2005; 59(3): 266-271.

Published online: 30 September 2005

DOI: https://doi.org/10.4046/trd.2005.59.3.266

Implication of embB Gene Mutation in Ethambutol-Susceptible Clinical Isolates of Mycobacterium tuberculosis

Young Kil Park, Ph.D.1, Sonya Shin, M.D.2, Sang Jae Kim, Ph.D.3, Won Jung Koh, M.D.4, O Jung Kwon, M.D.4, Bum Jun Kim, Ph.D.5, Yoon Ho Kook, Ph.D.5, Sang Nae Cho, Ph.D.6, Woo Jin Lew, M.D.1, Gill Han Bai, Ph.D.1

1Korean Institute of Tuberculosis, Seoul, Korea.

2Brigham and Women's Hospital Boston MA 02120, USA.

3International Union Against Tuberculosis and Lung Disease, Paris, France.

4Sungkyunkwan University of Medicine, Korea.

5Seoul National University College of Medicine, Korea.

6Yonsei University College of Medicine, Seoul, Korea.

Address for correspondence: Gill-Han Bai, Ph.D. Korean Institute of Tuberculosis 14 Woomyundong, Sochogu, Seoul, 137-900, Korea. Phone: 02-577-5766, Fax: 02-573-1914, gbai@hotmail.com

Received 26 May 2005       Accepted 29 August 2005

Copyright©2005. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

Ethambutol(EMB) is one of the first-line drugs included in short-course anti-tuberculosis therapy. The point mutations in embB gene have been speculated to be associated EMB resistance. However, detection of embB mutations at these positions have been observed in both EMB-susceptible isolates; thus, it remains controversial whether these mutations are associated with EMB resistance

Methods

The 36 M. tuberculosis isolates were selected from clinical isolates which tested susceptible to EMB and resistant to at least one drug. DNA extracted from the isolates was analyzed by amplifying embB gene. The PCR products were purified and directly sequenced. We reviewed the history of past drug susceptibility test results.

Results

Out of 36 EMB-susceptible strains, 3 strains (8.3%) had a mutation in codon 306 or 406 of the embB gene. These three strains had at least isoniazid resistance. They grew at 1.0 mcg/ml of EMB in Lowenstein-Jensen media. The patients of the strains were continuously smear-positive for over 3 years despite taking TB therapy. One strain had been EMB-resistant in past drug susceptibility tests.

Conclusion

EMB-susceptible strains containing embB mutation may be caused by decreased viability in vitro test not by itself.

Keywords: embB gene, Mutation, Ethambutol, Mycobacterium tuberculosis, Drug resistance, Korea

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