结核杆菌的药物外排泵

Research progress of drug efflux pumps in Mycobacterium tuberculosis

外排泵基因过度表达促使细胞内的药物转移到细胞外,胞内药物浓度下降,致使药物临床疗效降低或无效。外排泵上有多个与识别底物结构无关的阴离子凹穴(底物结合位点),通过静电引力非特异性结合各种含阳离子的药物,在能量协助下将药物排到细胞外,进而导致细菌抗药性的产生。研究表明,结核杆菌基因组中存在外排泵基因,但仅分离到几个有功效的外排泵。本文就相关研究进展进行综述。

Overexpression of efflux pump genes can increase the efflux of drugs,decrease the concentration of the intracellular drugs,resulting in reduced effect or inefficacy of clinical drugs.Efflux proteins having several concave holes（substrate binding sites）,which contain negative irons and are substrate-structurally unrelated,can unspecifically bind multiple positive iron drugs by electrostatic force,and efflux drugs out of the cell driven by energy gradient,conferring the cell multi-drug resistance.Researches showed that there was expression of drug efflux pumps in Mycobacterium tuberculosis.However,only several efflux pumps have been investigated and classified.This article reviewed the progress on this topic.