Development of pharmacophore models for AcrB protein and the identification of potential adjuvant candidates for overcoming efflux-mediated colistin resistance.

ABSTRACT: Growing multi-drug resistance (MDR) among ESKAPE pathogens is a huge challenge. Increased resistance to last-resort antibiotics, like colistin, has further aggravated this. Efflux is identified as a major route of colistin resistance. So, finding an FDA-approved efflux inhibitor for potential application as an adjuvant to colistin was the primary objective of this study. E. coli-AcrB pump inhibitors and substrates were used to develop and validate the pharmacophoric model. Drugs confirming this pharmacophore were subjected to molecular docking to identify hits for the AcrB binding pocket. The efflux inhibition potential of the top hit was validated through the in vitro evaluation of the minimum inhibitory concentration (MIC) in combination with colistin. The checkerboard assa

SUBMITTER: Behera DU 

PROVIDER: S-EPMC10809322 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature