Comparative Drug Resistance Reversal Potential of Natural Glycosides: Potential of Synergy Niaziridin & Niazirin
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Published:2019-07-19
Issue:10
Volume:19
Page:847-860
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ISSN:1568-0266
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Container-title:Current Topics in Medicinal Chemistry
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language:en
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Short-container-title:CTMC
Author:
Dwivedi Gaurav R.1, Maurya Anupam2, Yadav Dharmendra K.3, Khan Feroz3, Gupta Mahendra K.4, Gupta Prashant4, Darokar Mahendra P.1, Srivastava Santosh K.2
Affiliation:
1. Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, India 2. Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, India 3. Metabolic & Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, India 4. Department of Microbiology, King George Medical University, Lucknow, India
Abstract
Background:
Due to the limited availability of antibiotics, Gram-negative bacteria (GNB) acquire
different levels of drug resistance. It raised an urgent need to identify such agents, which can reverse the phenomenon
of drug resistance.
Objective:
To understand the mechanism of drug resistance reversal of glycosides; niaziridin and niazirin isolated
from the pods of Moringa oleifera and ouabain (control) against the clinical isolates of multidrug-resistant
Escherichia coli.
Methods:
The MICs were determined following the CLSI guidelines for broth micro-dilution. In-vitro combination
studies were performed by broth checkerboard method followed by Time-Kill studies, the efflux pump
inhibition assay, ATPase inhibitory activity, mutation prevention concentration and in-silico studies.
Results:
The results showed that both glycosides did not possess antibacterial activity of their own, but in combination,
they reduced the MIC of tetracycline up to 16 folds. Both were found to inhibit efflux pumps, but
niaziridin was the best. In real time expression pattern analysis, niaziridin was also found responsible for the
down expression of the two important efflux pump acrB & yojI genes alone as well as in combination.
Niaziridin was also able to over express the porin forming genes (ompA & ompX). These glycosides decreased
the mutation prevention concentration of tetracycline.
Conclusion:
This is the first ever report on glycosides, niazirin and niaziridin acting as drug resistance reversal
agent through efflux pump inhibition and modulation of expression pattern drug resistant genes. This study
may be helpful in preparing an effective antibacterial combination against the drug-resistant GNB from a
widely growing Moringa oleifera.
Funder
CIMAP in house project CSIR Network project and fellowships from Council of Scientific and Industrial Research
Publisher
Bentham Science Publishers Ltd.
Subject
Drug Discovery,General Medicine
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