Targeting efflux pumps to overcome antifungal drug resistance-Reference-Cited by-同舟云学术

Targeting efflux pumps to overcome antifungal drug resistance

Published:2016-08 Issue:12 Volume:8 Page:1485-1501
ISSN:1756-8919
Container-title:Future Medicinal Chemistry
language:en
Short-container-title:Future Medicinal Chemistry

Author:

Holmes Ann R¹,Cardno Tony S²³⁴,Strouse J Jacob⁵,Ivnitski-Steele Irena⁵,Keniya Mikhail V¹,Lackovic Kurt³⁴,Monk Brian C¹,Sklar Larry A⁵,Cannon Richard D¹

Affiliation:

1. Sir John Walsh Research Institute, University of Otago Faculty of Dentistry, PO Box 647, Dunedin 9054, New Zealand

2. Department of Biochemistry, University of Otago, PO Box 56, Dunedin 9054, New Zealand

3. Walter & Eliza Hall Institute of Medical Research Biotechnology Center, Melbourne, Australia

4. Department of Medical Biology, University of Melbourne, Parkville, Australia

5. New Mexico Center for Molecular Discovery, University of New Mexico, Albuquerque, New Mexico, USA

Abstract

Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps.

Publisher

Future Science Ltd

Subject

Drug Discovery,Pharmacology,Molecular Medicine

Link

http://www.future-science.com/doi/pdf/10.4155/fmc-2016-0050

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