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Modulatory effect of cAMP on fungal ergosterol level and inhibitory activity of azole drugs

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Abstract:

The functions and biosynthesis of sterols have been effective targets for fungal control in different areas, including pharmaceutical and agricultural applications. Fungi are among the organisms that synthesize sterols, principally ergosterol. In this paper, the effect of dibutyryl-cAMP (db-cAMP) on ergosterol level and the interaction of drugs that would change the concentration of cAMP with antifungal drugs have been investigated. Sterols were extracted from Candida albicans, and ergosterol was measured using the gas chromatography method. The interaction of different agents was measured by the broth dilution method. It was found that phosphodiesterase inhibitors reverse the inhibitory activity of azole antifungal drugs. Evaluating the ergosterol level of C. albicans incubated with db-cAMP revealed that it increased ergosterol level. Further experiments provided evidence attributing the observed interaction between azoles and phosphodiesterase inhibitors to the relationship between ergosterol and cAMP. The possible significance of this interaction includes potentiation of antifungal activity of drugs by manipulating the cAMP level.Key words: ergosterol, cAMP, phosphodiesterase inhibitor, antifungal.

Les fonctions et la biosynthèse des stérols sont des cibles efficaces pour le lutte contre les champignons dans différents secteurs incluant les applications pharmaceutiques et agricoles. Les champignons sont parmi les organismes capables de synthétiser des stérols, principalement l'ergostérol. Dans cet article, nous avons étudié l'influence du dibutyryl-AMPc (db-AMPc) sur les niveaux d'ergostérol ainsi que les interactions de composés qui changeraient la concentration d'AMPc avec des agents antifongiques. Les stérols de Candida albicans ont été extraits et l'egostérol fut dosé avec la méthode de chromatographie en phase gazeuse. L'interaction avec divers agents a été mesurée par la méthode de dilution en milieu liquide. Nous avons découvert que les inhibiteurs de phosphodiestérase annulent l'activité inhibitrice des agents antifongiques de type azole. Les niveaux d'ergostérol ont augmenté chez C. albicans incubé avec du db-AMPc. Des expériences subséquentes ont fourni des indices attribuant les interactions observées entre les azoles et les inhibiteurs de phosphodiestérase à la relation de l'ergostérol avec l'AMPc. Cette interaction pourrait être exploitée en manipulant les niveaux d'AMPc de manière à renforcer l'activité d'agents antifongiques.Mots clés : ergostérol, AMPc, inhibiteurs de phosphodiestérase, antifongiques.[Traduit par la Rédaction]

Document Type: Research Article

Publication date: May 1, 2003

More about this publication?
  • Published since 1954, this monthly journal contains new research in the field of microbiology including applied microbiology and biotechnology; microbial structure and function; fungi and other eucaryotic protists; infection and immunity; microbial ecology; physiology, metabolism and enzymology; and virology, genetics, and molecular biology. It also publishes review articles and notes on an occasional basis, contributed by recognized scientists worldwide.
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