结核分枝杆菌外排泵研究进展

Advances in study of efflux pumps of mycobacterium tuberculo

结核病是由结核分枝杆菌(Mycobacterium tuberculosis,Mtb)引起的一种传染病。随着多药耐药和广泛耐药结核分枝杆菌的出现,结核病的治疗变得更为艰难。近年来研究发现,结核分枝杆菌存在外排泵是其耐药的原因之一,现已发现结核分枝杆菌的主要易化子超家族(major facilitator superfamily,MFS)、三磷酸腺苷(adenosine-triphosphate,ATP)结合盒超家族(ATP-Binding Cassette,ABC)、耐受小节分裂区家族(resistance-nodulation-division,RND)和小耐多药性家族(small multidrug resistance,SMR)外排泵。但是人们对结核分枝杆菌外排泵介导的耐药现象认识不足,仍缺乏从新药发现角度研发外排泵抑制剂的研究。本文拟对结核分枝杆菌的ABC、MFS、RND和SMR外排泵的结构和功能,以及结核分枝杆菌外排泵抑制剂的研究进展进行综述。

Tuberculosis(TB)is an infectious disease caused by Mycobacterium tuberculosis(Mtb).With the emergence of multidrug-resistant TB(MDR-TB)and extensively drug-resistant TB(XDR-TB),the treatment of TB has become more severe.In recent years,studies have found that the existence of efflux pumps in Mycobacterium tuberculosis is one of the reasons for its drug resistance.The efflux pumps of major facilitator superfamily(MFS),ATP-Binding Cassette(ABC),resistance-nodulation-division(RND)and small multidrug resistance(SMR)have been found in Mtb.However,the drug resistance mediated by Mtb efflux pumps still remains largely unknown,and there is not much work to develop efflux pump inhibitors from the perspective of new drug discovery.This article reviews the structure and function of the efflux pumps of ABC,MFS,RND and SMR of Mtb,as well as the research progress of efflux pump inhibitors of Mtb.