Molecular Mechanisms of Resistance of Candida spp. to Membrane-targeting Antifungals
Luís A. Vale Silva
from: Antifungals: From Genomics to Resistance and the Development of Novel Agents (Edited by: Alix T. Coste and Patrick Vandeputte). Caister Academic Press, U.K. (2015) Pages: 1-26.
Abstract
Membrane-targeting antifungal drugs represent the most numerous group of available antifungals. Systemically available membrane-targeting drugs act either by inhibiting ergosterol biosynthesis or by binding ergosterol directly in the fungal cell membrane. Ergosterol biosynthesis inhibitors include the large group of azole drugs, as well as a few other drugs from three different chemical families: allylamines, morpholines and thiocarbamates. The sole representatives of ergosterol binding drugs are the polyenes, including two active compounds in clinical use: amphotericin B and nystatin. Various different mechanisms of resistance to membrane targeting drugs have been described. Resistance mechanisms may be grouped as alterations of the intracellular accumulation of the drug, of the drug target (target enzyme sequence alterations or upregulation), or of the sterol biosynthesis pathway. Often, different mechanisms combine in the same Candida spp. isolate, conferring stepwise increase in drug resistance. This chapter presents a review of the known mechanisms of resistance of Candida spp. to membrane-targeting antifungals currently in use to treat candidiasis read more ...
