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结核分枝杆菌泛耐药和耐多药菌株之间基因表达谱的比较。

Comparison of gene expression profiles between pansensitive and multidrug-resistant strains of Mycobacterium tuberculosis.

机构信息

Departamento de Biología Molecular, Centro de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Calle 2 de abril 501, Col. Independencia, 64720, Monterrey, Nuevo León, Mexico.

出版信息

Curr Microbiol. 2013 Sep;67(3):362-71. doi: 10.1007/s00284-013-0376-8. Epub 2013 May 7.

Abstract

Mycobacterium tuberculosis has developed resistance to anti-tuberculosis first-line drugs. Multidrug-resistant strains complicate the control of tuberculosis and have converted it into a worldwide public health problem. Mutational studies of target genes have tried to envisage the resistance in clinical isolates; however, detection of these mutations in some cases is not sufficient to identify drug resistance, suggesting that other mechanisms are involved. Therefore, the identification of new markers of susceptibility or resistance to first-line drugs could contribute (1) to specifically diagnose the type of M. tuberculosis strain and prescribe an appropriate therapy, and (2) to elucidate the mechanisms of resistance in multidrug-resistant strains. In order to identify specific genes related to resistance in M. tuberculosis, we compared the gene expression profiles between the pansensitive H37Rv strain and a clinical CIBIN:UMF:15:99 multidrug-resistant isolate using microarray analysis. Quantitative real-time PCR confirmed that in the clinical multidrug-resistant isolate, the esxG, esxH, rpsA, esxI, and rpmI genes were upregulated, while the lipF, groES, and narG genes were downregulated. The modified genes could be involved in the mechanisms of resistance to first-line drugs in M. tuberculosis and could contribute to increased efficiency in molecular diagnosis approaches of infections with drug-resistant strains.

摘要

结核分枝杆菌已对一线抗结核药物产生耐药性。耐多药菌株使结核病的控制变得复杂,并已将其转化为全球性公共卫生问题。针对靶基因的突变研究试图预测临床分离株中的耐药性;然而,在某些情况下,检测这些突变不足以确定耐药性,这表明还涉及其他机制。因此,识别新的一线药物敏感性或耐药性标志物可能有助于:(1) 专门诊断结核分枝杆菌菌株的类型并开出适当的治疗方法,以及 (2) 阐明耐多药菌株的耐药机制。为了鉴定结核分枝杆菌中与耐药性相关的特定基因,我们使用微阵列分析比较了泛敏感 H37Rv 菌株和临床 CIBIN:UMF:15:99 耐多药分离株之间的基因表达谱。实时定量 PCR 证实,在临床耐多药分离株中,esxG、esxH、rpsA、esxI 和 rpmI 基因上调,而 lipF、groES 和 narG 基因下调。修饰后的基因可能参与结核分枝杆菌对一线药物的耐药机制,并有助于提高耐药菌株感染的分子诊断方法的效率。

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