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分枝杆菌 vanbaalenii 作为研究结核分枝杆菌、海分枝杆菌和溃疡分枝杆菌药物转运蛋白的模式生物的潜力:分枝杆菌属中结核分枝杆菌药物转运蛋白的同源性分析。

Potential of Mycobacterium vanbaalenii as a model organism to study drug transporters of Mycobacterium tuberculosis, Mycobacterium marinum and Mycobacterium ulcerans: homology analysis of M. tuberculosis drug transporters among mycobacterial species.

机构信息

Department of Microbiology & Molecular Biology, National JALMA Institute for Leprosy & Other Mycobacterial Diseases (NJILOMD), Tajganj, Agra 282001, India.

出版信息

Infect Genet Evol. 2012 Jun;12(4):853-6. doi: 10.1016/j.meegid.2011.10.028. Epub 2011 Nov 23.

Abstract

Drug efflux pumps have been one of the important mechanisms of drug resistance in Mycobacterium tuberculosis. There is a prerequisite to study the behavior and mechanisms of these drug efflux pumps in detail for being considered in future anti-TB drug designing. The need of a rapid grower non-pathogenic mycobacterium with significant genomic homology for such type of studies is often being felt. During microarray and Real-Time PCR analysis of drug efflux pump genes of M. tuberculosis, we found 10 genes to be over-expressed during stress induced by common anti-TB drugs. In the present study homology analysis of these genes was done in order to know its phylogenetic relationship among other bacteria/mycobacteria. It was found that amino acid sequences of 7 out of 10 genes were significantly (>40%) identical to a non-pathogenic rapid grower environmental mycobacterium, Mycobacterium vanbaalenii. The protein sequences of M. vanbaalenii share important sequence motifs with M. tuberculosis useful for drug efflux mechanism based study across species. Like Mycobacterium smegmatis, it can be used as a model organism to study drug efflux pumps of M. tuberculosis and also other pathogenic mycobacteria such as Mycobacterium ulcerans and Mycobacterium marinum.

摘要

药物外排泵是结核分枝杆菌耐药的重要机制之一。为了在未来的抗结核药物设计中考虑这些药物外排泵的行为和机制,有必要详细研究它们。通常需要一种具有重要基因组同源性的快速生长非致病性分枝杆菌来进行此类研究。在结核分枝杆菌药物外排泵基因的微阵列和实时 PCR 分析中,我们发现 10 个基因在常见抗结核药物诱导的应激下过度表达。在本研究中,对这些基因进行了同源性分析,以了解它们在其他细菌/分枝杆菌中的系统发育关系。结果发现,其中 7 个基因的氨基酸序列与一种非致病性、快速生长的环境分枝杆菌——分枝杆菌 vanbaalenii 有显著的相似性(>40%)。分枝杆菌 vanbaalenii 的蛋白序列与结核分枝杆菌共享重要的序列基序,可用于跨物种的药物外排机制研究。像分枝杆菌 smegmatis 一样,它可以作为一种模式生物来研究结核分枝杆菌和其他致病性分枝杆菌(如溃疡分枝杆菌和海分枝杆菌)的药物外排泵。

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