Correlation of inhibition of sterol synthesis with growth-inhibitory action of imidazole antimycotics in Candida albicans.
The effect of tioconazole and other imidazole antimycotics on both growth and sterol biosynthesis by Candida albicans and C. pseudotropicalis in tube culture was investigated. Trailing endpoints were only seen in statically incubated cultures, but the final MIC, i.e. that giving complete inhibition of growth, was similar in both static and shaken cultures. Desmethylsterol biosynthesis was equally sensitive to the inhibitory action of tioconazole in both shaken and static cultures and the trailing endpoints in the latter coincided with this inhibition. Poor inhibitors of ergosterol biosynthesis did not show the trailing phenomenon but did show a conventional MIC. The inhibition of sterol biosynthesis, unlike that of growth, was not subject to an inoculum effect. As others have found, ergosterol was unable to antagonize the effects of tioconazole on C. albicans and this was probably due to lack of uptake of this sterol. In contrast to C. albicans, the Gram-positive bacterium, Staphylococcus aureus H, which lacks membrane sterols, showed no trailing endpoints with tioconazole after either shaken or static incubation.
Nicholas
R O
RO
Department of Biochemistry, University of Cambridge, UK.
Kerridge
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D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development*; D004875:Ergosterol / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013261:Sterols / Q000096:biosynthesis*
D000935:Antifungal Agents; D007093:Imidazoles; D013261:Sterols; D008825:Miconazole; D007654:Ketoconazole; C020527:tioconazole; D004875:Ergosterol