Cross resistance of fluoroquinolone drugs on gyrA gene mutation in Mycobacterium tuberculosis

Young Kil Park, Chan Hong Park, Won Jung Koh, O. Jung Kwon, Bum Jun Kim, Yoon Hoh Kook, Sangnae Cho, Chulhun Chang, Gill Han Bai

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)250-256
Number of pages7
JournalTuberculosis and Respiratory Diseases
Volume59
Issue number3
DOIs
Publication statusPublished - 2005 Jan 1

Fingerprint

Ofloxacin
Fluoroquinolones
Mycobacterium tuberculosis
Drug Resistance
Mutation
Genes
Levofloxacin
Ciprofloxacin
Multidrug-Resistant Tuberculosis
Point Mutation
Codon
Pharmaceutical Preparations
moxifloxacin
gatifloxacin
sparfloxacin
DNA
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Infectious Diseases

Cite this

Park, Y. K., Park, C. H., Koh, W. J., Kwon, O. J., Kim, B. J., Kook, Y. H., ... Bai, G. H. (2005). Cross resistance of fluoroquinolone drugs on gyrA gene mutation in Mycobacterium tuberculosis. Tuberculosis and Respiratory Diseases, 59(3), 250-256. https://doi.org/10.4046/trd.2005.59.3.250
Park, Young Kil ; Park, Chan Hong ; Koh, Won Jung ; Kwon, O. Jung ; Kim, Bum Jun ; Kook, Yoon Hoh ; Cho, Sangnae ; Chang, Chulhun ; Bai, Gill Han. / Cross resistance of fluoroquinolone drugs on gyrA gene mutation in Mycobacterium tuberculosis. In: Tuberculosis and Respiratory Diseases. 2005 ; Vol. 59, No. 3. pp. 250-256.
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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.",
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Cross resistance of fluoroquinolone drugs on gyrA gene mutation in Mycobacterium tuberculosis. / Park, Young Kil; Park, Chan Hong; Koh, Won Jung; Kwon, O. Jung; Kim, Bum Jun; Kook, Yoon Hoh; Cho, Sangnae; Chang, Chulhun; Bai, Gill Han.

In: Tuberculosis and Respiratory Diseases, Vol. 59, No. 3, 01.01.2005, p. 250-256.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cross resistance of fluoroquinolone drugs on gyrA gene mutation in Mycobacterium tuberculosis

AU - Park, Young Kil

AU - Park, Chan Hong

AU - Koh, Won Jung

AU - Kwon, O. Jung

AU - Kim, Bum Jun

AU - Kook, Yoon Hoh

AU - Cho, Sangnae

AU - Chang, Chulhun

AU - Bai, Gill Han

PY - 2005/1/1

Y1 - 2005/1/1

N2 - 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.

AB - 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.

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