| Literature DB >> 27463566 |
Ann R Holmes1, Tony S Cardno2,3,4, J Jacob Strouse5, Irena Ivnitski-Steele5, Mikhail V Keniya1, Kurt Lackovic3,4, Brian C Monk1, Larry A Sklar5, Richard D Cannon1.
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.Entities:
Keywords: ABC and MFS transporters; antifungal drug resistance; azole; chemosensitization; heterologous expression; high-throughput screen
Mesh：
Substances：
Year: 2016 PMID： 27463566 PMCID： PMC5827819 DOI： 10.4155/fmc-2016-0050
Source DB: PubMed Journal: Future Med Chem ISSN： 1756-8919 Impact factor: 3.808