결핵균에서 gyrA 유전자 돌연변이에 따른 fluoroquinolone계 약제들의 교차내성

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 3킽/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.