임상에서 분리된 에탐부톨 감수성균에서의 embB 유전자 돌연변이에 대한 고찰
Implication of embB Gene Mutation in Ethambutol-Susceptible Clinical Isolates of Mycobacterium tuberculosis
류우진 (대한결핵협회 결핵연구원)
고원중 (성균관대학교)
조상래 (연세대학교)
김상재 (대한결핵협회 결핵연구원)
권오정 (성균관대학교)
국윤호 (서울대학교)
배길한 (대한결핵협회 결핵연구원)
김범준 (서울대학교)
Sonya Shin (Brigham and Women's Hospital)
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초록
배 경 : 에탐부톨은 6개월 단기요법 중에 사용되는 1차 항결핵약제 중 하나이다. embB 유전자의 돌연변이는 에탐부톨의 내성과 관련이 있은 것으로 추측 되어 왔다. 그러나 최근에 embB 유전자의 돌연변이는 에탐부톨 감수성인 균에서도 발견되어 이 유전자의 돌연변이가 에탐부톨 내성과 관련이 있는 것인지에 대한 논란이 있는 바, 이에 대한 이해를 높이고자 본 실험을 하게 되었다.방 법 : 약제감수성검사에서 에탐부톨은 감수성이지만 타 항결핵약제에 내성을 보인 36균주를 선택하였다. 이 균주들에서 embB 유전자에 대하여 중합효소연쇄반응를 실시한 후에 염기서열분석을 통해 돌연변이 여부를 조사하였다. 돌연변이가 있는 균주에 대하여 과거의 항결핵약제 감수성검사 결과를 비교하였다.
- keywords
- embB gene, Mutation, Ethambutol, Mycobacterium tuberculosis, Drug resistance, Korea, embB gene, Mutation, Ethambutol, Mycobacterium tuberculosis, Drug resistance, Korea
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. (Tuberc Respir Dis 2005; 59: 266-271)
- keywords
- embB gene, Mutation, Ethambutol, Mycobacterium tuberculosis, Drug resistance, Korea, embB gene, Mutation, Ethambutol, Mycobacterium tuberculosis, Drug resistance, Korea
참고문헌
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