PMID: 22353004Feb 23, 2012Paper

Bacterial efflux pumps involved in multidrug resistance and their inhibitors: rejuvinating the antimicrobial chemotherapy

Recent Patents on Anti-infective Drug Discovery
Ashima Kushwaha Bhardwaj, Priyabrata Mohanty

Abstract

Active efflux of antibiotics is one of the major mechanisms of drug resistance in bacteria. The efflux process is mediated by membrane transporters with a large variety of unrelated compounds as their substrates. Though these pumps are responsible for the low intrinsic resistance of a bacterium to a drug, their overexpression, accumulation of mutations in these proteins and their synergy with other drug resistance mechanisms hampers effective antimicrobial treatment. As efflux pumps have been reported to play vital roles in mediating multidrug resistance in clinical isolates from varied geographic locations and varied populations, the inhibition of efflux pumps appears to be an attractive approach to combat the problem of drug resistance. Efflux pump inhibitors can be utilized for increasing the antibiotic concentration inside a pathogenic cell making these drugs more effective, reduce the accumulation of other resistance mechanisms in a cell and for diagnostic purposes to evaluate the presence and contribution of the efflux mechanism in a pathogen. A large number of inhibitors have been discovered and patented in last two decades but the process of discovery, testing and commercialization is rather slow. Some of the important ...Continue Reading

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