Microbiology

Assessing Antifungals

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Science  26 May 2000:
Vol. 288, Issue 5470, pp. 1301-1303
DOI: 10.1126/science.288.5470.1301e

The activity of a candidate drug is normally determined in vitro with a purified target molecule. But drug effects on a specific target can perturb linked metabolic pathways in surprising and complex ways.

Bammert and Fostel have used DNA microarrays to assess the response of the yeast Saccharomyces cerevisiae to previously characterized azole antifungals known to target enzymes in the ergosterol biosynthetic pathway. In addition to effects on expression of these enzymes, they found what appear to be secondary effects on the transcription of genes involved in mitochondrial function, reaction to oxidative stress, and heme biosynthesis. A structurally distinct imidazole-containing compound produced a similar expression pattern to that of the established azole drugs, suggesting a similar mode of action and offering a high-throughput approach to finding alternatives to circumvent the increasingly serious problem of azole drug resistance among opportunist fungal pathogens, such as Candida albicans.CA

Antimicrob. Agents Chemother.44, 1255 (2000).

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