Reduced accumulation of drug in Candida krusei accounts for itraconazole resistance

K. Venkateswarlu, David W. Denning, Nigel J. Manning, Steven L. Kelly

Research output: Contribution to journalArticlepeer-review

Abstract

Due to intrinsic resistance Candida krusei is emerging as a systemic pathogen in AIDS patients undergoing fluconazole therapy, but acquired resistance to itraconazole has not been studied biochemically. We report here studies on the basis for azole resistance and sterol composition in C. krusei. An itraconazole-resistant isolate showed reduced susceptibility to azole drugs in in vitro growth inhibition studies. Accumulation of 14α- methyl-3,6-diol under azole treatment was associated with growth arrest. In vitro ergosterol biosynthesis and type II binding studies suggested no alteration in the affinity to azole drugs of the target enzyme, the cytochrome P-450 sterol 14α-demethylase, in the resistant isolate. Resistance was associated with a decreased intracellular content of drug in the resistant isolate.

Original languageEnglish
Pages (from-to)2443-2446
Number of pages4
JournalAntimicrobial Agents and Chemotherapy
Volume40
Issue number11
Publication statusPublished - 1 Nov 1996

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