https://scholars.lib.ntu.edu.tw/handle/123456789/452144
標題: | Inhibition of the Mycobacterium tuberculosis reserpine-sensitive efflux pump augments intracellular concentrations of ciprofloxacin and enhances susceptibility of some clinical isolates | 作者: | Huang T.-S. Kunin C.M. Wang H.-M. BO-SHIUN YAN Huang S.-P. Chen Y.-S. Shin-Jung Lee S. Syu W.-J. |
關鍵字: | Efflux; Fluoroquinolones; Mycobacterium tuberculosis | 公開日期: | 2013 | 卷: | 112 | 期: | 12 | 起(迄)頁: | 789-794 | 來源出版物: | Journal of the Formosan Medical Association | 摘要: | Background/Purpose: Active efflux is known to play a major role in the resistance of many bacteria to antibiotics. To evaluate the possibility of overcoming resistance by suppressing the efflux, we determined the effect of reserpine, an efflux pump inhibitor. Methods: Intracellular accumulations and the minimal inhibitory concentrations (MICs) of ciprofloxacin in M. tuberculosis H37Rv and 16 clinical isolates were determined, compared, and analyzed. Nine of the clinical isolates were resistant to isoniazid and rifampin (multiple-drug resistant MDR). Five of these were resistant to ciprofloxacin. Results: A reserpine-inhibited efflux system was identified in the H37Rv control and 10:1 (90.9%) of ciprofloxacin-susceptible and 4:1 (80%) of ciprofloxacin-resistant clinical isolates. The MIC of ciprofloxacin decreased in the presence of reserpine in 3/10 (30%) of the ciprofloxacin-susceptible and 2/4 (50%) of the MDR ciprofloxacin-resistant strains that expressed efflux pumps. Two of the efflux-positive, ciprofloxacin-resistant strains in which the MIC of ciprofloxacin was not decreased by reserpine were found to carry a D94A gyrA mutation. In contrast, two strains with the D94G gyrA mutation were susceptible to ciprofloxacin in the presence of reserpine. An efflux-negative strain, highly resistant to multiple antibiotics, was found to have a novel G247S mutation that differs from known mutations in the QRDR region of the gyrA gene. Conclusion: These findings indicate t hat reserpine can increase intracellular concentrations of ciprofloxacin, but is unable to overcome other mechanisms of resistance in clinical isolates. ? 2012. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84890231090&doi=10.1016%2fj.jfma.2012.03.009&partnerID=40&md5=77197c125bc0146c76eb99cda494abe3 https://scholars.lib.ntu.edu.tw/handle/123456789/452144 |
ISSN: | 9296646 | DOI: | 10.1016/j.jfma.2012.03.009 | SDG/關鍵字: | aminosalicylic acid; antibiotic agent; ciprofloxacin; isoniazid; kanamycin; levofloxacin; moxifloxacin; ofloxacin; reserpine; rifampicin; adrenergic receptor affecting agent; antiinfective agent; ciprofloxacin; DNA topoisomerase (ATP hydrolysing); reserpine; antibiotic resistance; antibiotic sensitivity; article; bacterial gene; bacterial genetics; bacterial strain; bacterium isolate; controlled study; dose response; drug effect; gene mutation; gyrA gene; gyrB gene; minimum inhibitory concentration; multidrug resistance; Mycobacterium tuberculosis; cell membrane permeability; drug effects; genetics; microbial sensitivity test; mutation; Mycobacterium tuberculosis; Adrenergic Uptake Inhibitors; Anti-Bacterial Agents; Cell Membrane Permeability; Ciprofloxacin; DNA Gyrase; Drug Resistance, Bacterial; Microbial Sensitivity Tests; Mutation; Mycobacterium tuberculosis; Reserpine |
顯示於: | 生物化學暨分子生物學科研究所 |
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