Submit Manuscript  

Article Details


Comparative Drug Resistance Reversal Potential of Natural Glycosides Synergy Potential of Niaziridin & Niazirin

Author(s):

Gaurav Raj Dwivedi, Anupam Maurya, Dharmendra Kumar Yadav, Feroz Khan, Mahendra Kumar Gupta, Prashant Gupta, Mahendra P. Darokar* and Santosh Kumar Srivastava*   Pages 1 - 13 ( 13 )

Abstract:


Due to 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. The present study was intended to understand the mechanism of drug resistance reversal of glycosides namely niaziridin, niazirinisolated from Moringaoleiferaand ouabain (control)against clinical isolates of multidrug resistant Escherichia coli (MDREC).As per stringent antibacterial criteria, these glycosides did not possess any significant antibacterial activity of its own, but in combination, they reduced the minimum inhibitory concentration (MIC) of tetracycline (TET) up to 16 folds. Glycosides namely niaziridin and niazirinwas found to inhibit efflux pumps as evident by efflux pump inhibition assay, ATPase inhibition assay and in silico docking studies.It was also evident from above assays, among the above glycosides;niaziridinwas the best efflux pump inhibitor.In real time expression pattern analysis, niaziridin was also responsible for down expression of two important efflux pump acrB&yojIgenes 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 (MPC) of tetracycline.This is for the first report on the glycosides (niazirin and niaziridin) as drug resistance reversal agent acting through efflux pump inhibition and modulation of expression pattern drug resistance genes. This study will be helpful in to build aneffective antibacterial combination from widely growing Moringaoleiferaagainst drug resistant GNB.

Keywords:

MDR, Glycosides, niaziridin, niazirin, antibacterial combinations

Affiliation:

Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Metabolic & Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Metabolic & Structural Biology, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Department of Microbiology, King George Medical University, Lucknow, Department of Microbiology, King George Medical University, Lucknow, Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015, Medicinal Chemistry Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow-226015



Read Full-Text article