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Tuberculosis & Respiratory Diseases

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Vol.59 No.3
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결핵균에서 gyrA 유전자 돌연변이에 따른 Fluoroquinolone계 약제들의 교차내성

Cross Resistance of Fluoroquinolone Drugs on gyrA Gene Mutation in Mycobacterium tuberculosis

Tuberculosis & Respiratory Diseases / Tuberculosis & Respiratory Diseases,
2005, v.59 no.3, pp.250-256
박영길 (대한결핵협회 결핵연구원)
김범준 (서울대학교)
권오정 (성균관대학교)
국윤호 (서울대학교)
조상래 (연세대학교)
배길한 (대한결핵협회 결핵연구원)
고원중 (성균관대학교)
박찬홍 (결핵연구원)
장철훈 (부산대학교)
박영길, 김범준, 권오정, 국윤호, 조상래, 배길한, 고원중, 박찬홍, & 장철훈. (2005). 결핵균에서 gyrA 유전자 돌연변이에 따른 Fluoroquinolone계 약제들의 교차내성. Tuberculosis & Respiratory Diseases, 59(3), 250-256.
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초록

배 경 :FQ계 약제는 다제내성 결핵환자들의 치료를 위한 주용 2차 항결핵약제의 하나이다. 그러나 FQ계 여러 약제들 간 교차내성정도와 내성관련 유전자인 gyrA의 돌연변이간 관련성을 조사하게 되었다.방 법 :결핵균 중에서 OFX 내성인 63균주와 감수성인 10균주를 대상으로 Lowenstein-Jensen 배지에 CIP, LVX, MXF, GAT, SPX 등에 대한 교차내성을 조사하였다. 퀴놀론계 각 약제를 0.5-3g/ml 농도로 첨가한 배지에서, 2g/ml 이상에서 균이 발육한 경우를 내성으로 판정하였다. OFX 내성인 균주의 gyrA 및 gyrB 유전자의 돌연변이가 잘 발생하는 곳을 염기서열 분석하여 약제별로 그 교차내성 양상을 비교하였다.

keywords
Mycobacterium tuberculosis, Fluoroquinolones, Cross resistance, gyrA, Genotypes, Mycobacterium tuberculosis, Fluoroquinolones, Cross resistance, gyrA, Genotypes

Abstract

Background : Fluoroquinolone drugs are an important anti-tuberculous agent for the treatment of multi-drug resistant tuberculosis. However, many drugs belonging to the fluoroquinolones have different cross resistance to each other.         Methods : Sixty-three ofloxacin (OFX) resistant and 10 pan-susceptible M. tuberculosis isolates were selected, and compared for their cross resistance using a proportion method on Lowenstein-Jensen media, containing ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), moxifloxacin (MXF), gatifloxacin (GAT) and sparfloxacin (SPX), at concentrations ranging from 0.5 to 3µg/ml. DNA extracted from the isolates was directly sequenced after amplifying from the gyrA and gyrB genes.    Results : The 63 OFX resistant M. tuberculosis isolates showed complete cross resistance to CIP, but only 90.5, 44.4, 36.5 and 46.0% to LVX, MXF, GAT, and to SPX, respectively. Fifty-one of the isolates (81.0%) had point mutations in codons 88, 90, 91 and 94 in gyrA, which are known to be correlated with OFX resistance. The Gly88Ala, Ala90Valand Asp94Ala mutations in gyrA showed a tendency to be susceptible to MXF, GAT and SPX. Only 4 isolates had mutations in the gyrB gene, which did not affect the OFX resistance.    Conclusion : About 60% of the OFX resistant M. tuberculosis isolates were susceptible to GAT, SPX and MXF. These fluoroquinolones may be useful in the treatment of TB patients showing OFX resistance. (Tuberc Respir Dis 2005; 59: 250-256)

keywords
Mycobacterium tuberculosis, Fluoroquinolones, Cross resistance, gyrA, Genotypes, Mycobacterium tuberculosis, Fluoroquinolones, Cross resistance, gyrA, Genotypes

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Tuberculosis & Respiratory Diseases

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