大肠杆菌耐药机制中激活外排泵和减少摄入量的研究进展

The Research on the Activation of Multidrug Efflux Pumps and the Reduction of Intakes of the E.coli Drug-resistant Mechanisms

概述了大肠杆菌中激活外排泵和减少摄入量这两个重要的耐药机制和克服它们的新策略,主要包括近年来在理解外排泵系统的物理结构、功能和调控子中的进步和有利于开发以外排泵为靶位的药物研究进展。

Antibiotic resistance of bacterial pathogens is a fast emerging global crisis and an understanding of the underlying resistance mechanisms is paramount for design and development of new therapeutic strategies.Permeability barriers for and active efflux of drug molecules are two resistance mechanisms that have been implicated in various infectious outbreaks of antibiotic resistant pathogens,suggesting that these mechanisms may be good targets for new drugs.The synergism of reduced uptake and efflux is most evident in the multiplicative action of the outer membrane permeability barrier and active efflux,which results in high-level intrinsic and/or acquired resistance in many clinically important Gram-negative bacteria.This review summarizes the current knowledge of these two important resistance mechanisms and potential strategies to overcome them.Recent advances in understanding the physical structures,function and regulation of efflux systems will facilitate exploitation of pumps as new drug targets.