Simvastatin inhibits Candida albicans biofilm in vitro.
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 by >90% 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.
Liu
Geoffrey
G
Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut 06520, USA.
Vellucci
Vincent F
VF
Kyc
Stephanie
S
Hostetter
Margaret K
MK
D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000096:biosynthesis; D066298:In Vitro Techniques; D019821:Simvastatin / Q000494:pharmacology*; D013053:Spectrophotometry
D019821:Simvastatin; D004875:Ergosterol