Simvastatin Inhibits Candida albicans Biofilm In Vitro
| Autor: | Geoffrey Liu, Margaret K. Hostetter, Stephanie Kyc, Vincent F. Vellucci |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Simvastatin
In Vitro Techniques Biology Microbiology chemistry.chemical_compound Biosynthesis Ergosterol Candida albicans polycyclic compounds medicine Dose-Response Relationship Drug Biofilm nutritional and metabolic diseases biochemical phenomena metabolism and nutrition biology.organism_classification Sterol Yeast chemistry Biochemistry Spectrophotometry Biofilms Pediatrics Perinatology and Child Health HMG-CoA reductase biology.protein lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Pediatric Research. 66:600-604 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/pdr.0b013e3181bd5bf8 |
| Popis: | By inhibiting the conversion of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) to mevalonate, statins impair cholesterol metabolism in humans. We reasoned that statins might similarly interfere with the biosynthesis of ergosterol, the major sterol of the yeast cell membrane. As assessed by spectrophotometric and microscopic analysis, significant inhibition of biofilm production was noted after 16-h incubation with 1, 2.5, and 5 muM simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 muM simvastatin) inhibited biofilm by90% but also impaired growth. Addition of exogenous ergosterol (90 muM) overcame the effects of 1 and 2.5 muM simvastatin, suggesting that at least one mechanism of inhibition is interference with ergosterol biosynthesis. Clinical isolates from blood, skin, and mucosal surfaces produced biofilms; biofilms from bloodstream isolates were similarly inhibited by simvastatin. In the absence of fungicidal activity, simvastatin's interruption of a critical step in an essential metabolic pathway, highly conserved from yeast to man, has unexpected effects on biofilm production by a eukaryotic pathogen. |
| Databáze: | OpenAIRE |
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