Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance

Shriram, V, Khare, T, Bhagwat, R, Shukla, R and Kumar, V 2018, 'Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance', Frontiers in Microbiology, vol. 9, pp. 1-35.


Document type: Journal Article
Collection: Journal Articles

Title Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance
Author(s) Shriram, V
Khare, T
Bhagwat, R
Shukla, R
Kumar, V
Year 2018
Journal name Frontiers in Microbiology
Volume number 9
Start page 1
End page 35
Total pages 35
Publisher Frontiers Research Foundation
Abstract Antibiotics, once considered the lifeline for treating bacterial infections, are under threat due to the emergence of threatening antimicrobial resistance (AMR). These drug-resistant microbes (or superbugs) are non-responsive to most of the commonly used antibiotics leaving us with few treatment options and escalating mortality-rates and treatment costs. The problem is further aggravated by the drying-pipeline of new and potent antibiotics effective particularly against the AMR strains. Multidrug efflux pumps (EPs) are established as principal determinants of AMR, extruding multiple antibiotics out of the cell, mostly in non-specific manner and have therefore emerged as potent drug-targets for combating AMR. Plants being the reservoir of bioactive compounds can serve as a source of potent EP inhibitors (EPIs). The phyto-therapeutics with noteworthy drug-resistance-reversal or re-sensitizing activities may prove significant for reviving the otherwise fading antibiotics arsenal and making this combination-therapy effective. Contemporary attempts to potentiate the antibiotics with plant extracts and pure phytomolecules have gained momentum though with relatively less success against Gram-negative bacteria. Plant-based EPIs hold promise as potent drug-leads to combat the EPI-mediated AMR. This review presents an account of major bacterial multidrug EPs, their roles in imparting AMR, effective strategies for inhibiting drug EPs with phytomolecules, and current account of research on developing novel and potent plant-based EPIs for reversing their AMR characteristics. Recent developments including emergence of in silico tools, major success stories, challenges and future prospects are also discussed.
Subject Nanobiotechnology
Keyword(s) Antimicrobial resistance (AMR)
drug efflux pumps
Efflux pump inhibitors
MDR
XDR
PDR
molecular docking
DOI - identifier 10.3389/fmicb.2018.02990
Copyright notice Copyright © 2018 Shriram, Khare, Bhagwat, Shukla and Kumar. Creative Commons Attribution License (CC BY).
ISSN 1664-302X
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