Antituberculosis drugs: reducing efflux = increasing activity. Issue 3 (March 2017)

• Record Type: Journal Article
• Authors: Rodrigues, Liliana; Parish, Tanya; Balganesh, Meenakshi; Ainsa, José A.
• Is Part Of: Drug discovery today. Volume 22:Issue 3(2017)
• Page Start: 592
• Page End: 599
• Publication Date: 2017-03
• Subjects: Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2017.01.002
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Efflux pumps are membrane proteins involved in the transport of antimicrobial drugs. Inhibition of efflux systems can prevent drug resistance. Strategies to avoid resistance by efflux should be included in TB drug discovery. Abstract : In mycobacteria, it was assumed that efflux pumps only had a marginal role in drug resistance. In recent years, owing to the need to find novel drugs against multidrug-resistant tuberculosis, it has become clear that efflux should not be ignored. Although efflux inhibitors have been very useful for characterizing in vitro the properties of efflux pumps, their usefulness in vivo is limited because of their toxicity. Alternatively, programs aimed at discovering novel drugs for treating tuberculosis should implement strategies to characterize efflux liability of candidate drugs. Here, we present an experimental approach for studying efflux of compounds selected under the More Medicines for Tuberculosis research project, and a few examples of how, for tuberculosis drug discovery, efflux matters.