The hydrophobic trap-the Achilles heel of RND efflux pumps

被引：40

作者：

Aron, Zachary ^{[1
]}

Opperman, Timothy J. ^{[1
]}

机构：

[1] Microbiotix Inc, One Innovat Dr, Worcester, MA 01605 USA

来源：

RESEARCH IN MICROBIOLOGY | 2018年 / 169卷 / 7-8期

关键词：

RND superfamily; Efflux pump; Efflux pump inhibitor; Adjunctive therapy; Hydrophobic trap; ENTERICA SEROVAR TYPHIMURIUM; MULTIDRUG TRANSPORTER ACRB; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA; ANTIBIOTIC-RESISTANCE; ROTATING MECHANISM; BIOFILM FORMATION; ESCHERICHIA-COLI; IN-VIVO; INHIBITORS;

D O I：

10.1016/j.resmic.2017.11.001

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Resistance-nodulation-division (RND) superfamily efflux pumps play a major role in multidrug resistance (MDR) of Gram-negative pathogens by extruding diverse classes of antibiotics from the cell. There has been considerable interest in developing efflux pump inhibitors (EPIs) of RND pumps as adjunctive therapies. The primary challenge in EPI discovery has been the highly hydrophobic, poly-specific substrate binding site of the target. Recent findings have identified the hydrophobic trap, a narrow phenylalanine-lined groove in the substrate-binding site, as the "Achilles heel" of the RND efflux pumps. In this review, we will examine the hydrophobic trap as an EPI target and two chemically distinct series of EPIs that bind there. (C) 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

引用

页码：393 / 400

页数：8

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