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耐药和敏感结核分枝杆菌临床分离株及参考株中外排泵基因的表达分析。

Expression analysis of efflux pump genes among drug-susceptible and multidrug-resistant Mycobacterium tuberculosis clinical isolates and reference strains.

机构信息

Microbiology Department, Faculty of Medicine, Ankara University, 06100 Sihhiye-Ankara, Turkey.

出版信息

Diagn Microbiol Infect Dis. 2013 Jul;76(3):291-7. doi: 10.1016/j.diagmicrobio.2013.02.033. Epub 2013 Apr 2.

Abstract

Finding a gene or genes that are involved with multidrug resistance will be useful for finding a new target for the treatment of drug resistant tuberculosis. In this study, we aimed to compare the differences of the expression of 15 putative multidrug efflux pump genes in clinically isolated drug sensitive and multidrug resistant (MDR) Mycobacterium tuberculosis isolates, and reference strains. We found that these genes in the drug-sensitive and MDR M. tuberculosis isolates have similar rates of expressions. However, we found the expression levels of the all the genes are significantly higher in the clinical strains compared to the expression level of genes in the reference strains. In addition to this, it is found that standard strain has lower MIC value for the drugs including streptomycin and rifampin compared to the clinical isolate. We presume that the increase of the gene expression in the clinical strains is due to the exposure of antituberculosis drugs during treatment of patients, which cause constitutive expression of efflux systems, which might increase MIC levels of the major anti-tuberculosis drugs.

摘要

找到与多药耐药性相关的基因或基因将有助于为治疗耐药性肺结核找到新的靶点。在这项研究中,我们旨在比较临床分离的药敏和多药耐药(MDR)结核分枝杆菌分离株和参考株中 15 个推定的多药外排泵基因表达的差异。我们发现这些基因在药敏和 MDR 结核分枝杆菌分离株中的表达率相似。然而,我们发现与参考株中的基因表达水平相比,临床株中所有基因的表达水平都显著升高。除此之外,还发现标准株对链霉素和利福平等药物的 MIC 值低于临床分离株。我们推测,临床株中基因表达的增加是由于在治疗患者过程中暴露于抗结核药物,导致外排系统的组成性表达,这可能会增加主要抗结核药物的 MIC 水平。

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