期刊
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
卷 1794, 期 5, 页码 826-833出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbapap.2008.12.011
关键词
AcrAB-TolC; Antibiotic; Efflux pump; Chemosensitizer; Efflux pump inhibitor; Membrane channel; MexAB-OprM; Multidrug resistance; Gram negative bacteria; Transporter
资金
- Universite de la Mediterranee and Service de Sante des Armees
Chemoresistance presents a general health problem concerning the therapy of infectious disease and cancer. In this context, the worldwide dissemination of multidrugresistant (MDR) pathogens has severely reduced the efficacy of our antimicrobial weapons and dramatically increased the frequency of therapeutic failure. Because MDR bacterial infections involve the over-expression of efflux pumps that expel unrelated antibiotics before they can reach their targets, it is necessary to clearly define the molecular and genetic bases of the MDR mechanisms in order to combat these infectious diseases. This characterization of efflux pumps allows the definition of an original anti-resistance weapon, the efflux pump inhibitor (EPI). Several chemical families of EPIs have been now described and characterized. Among them several inhibitor compounds display an efficient activity and inhibit the major AcrAB-TolC and MexAB-OprM efflux systems which are the major efflux pumps responsible for MDR Gram negative clinical isolates. The use of these EPIs induces a significant reduction of resistance to one or more antibiotics to which these isolates were initially resistant. Hence, the EPI when used as an adjuvant to the given antibiotic, restores the activity of the antibiotic. The description of the responsible efflux mechanism at its structural and physiological level will make it possible to develop along intelligent lines an improved new generation of EPIs that can readily be added to the armamentarium of current and past fallen by the wayside antibiotic therapies. (C) 2009 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据