Simvastatin Inhibits Candida albicans Biofilm In Vitro

Abstract

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 M simvastatin, concentrations that did not affect growth, adhesion, or hyphal formation by C. albicans in vitro. Higher concentrations (10, 20, and 25 M simvastatin) inhibited biofilm by Ͼ90% but also impaired growth. Addition of exogenous ergosterol (90 M) overcame the effects of 1 and 2.5 M 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. (Pediatr Res 66: 600-604, 2009)

Systematic review of the in vitro effects of statins on oral and perioral microorganisms

“…The mechanism of antifungal activity against Candida , Aspergillus spp., and Zygomycetes spp. is not clear, but it is likely to be caused by the interference of the ergosterol cycle and the disruption of the fungal cell wall. Statins also indirectly affect cell signaling , proliferation, and differentiation through inhibition of isoprenoid synthesis .…”

Fungal Biofilm Resistance

“…Overall, these data highlight the importance of ergosterol in biofilm resistance, particularly with respect to azoles, which indirectly inhibit their biosynthesis. Recent studies have shown that simvastatin, which impairs cholesterol metabolism in humans, is capable of inhibiting C. albicans biofilms, thus providing a potential novel strategy of combating these tenacious infections [122]. …”

Plasma membrane lipids and their role in fungal virulence

“…Ergosterol appears to be essential for the formation of biofilms; however, as shown by Mukherjee et al[83] ergosterol levels dropped to almost half of their initial concentration after 48 hours of biofilm maturation. The importance of ergosterol for biofilm formation was shown in the study of Liu et al[84], where addition of simvastatin (a compound with inhibitory effect on ergosterol biosynthesis[85]) was reported to inhibit the formation of C. albicans biofilms. Interestingly, the effect of low simvastatin concentrations could be reversed by addition of exogenous ergosterol suggesting the importance of ergosterol in biofilm formation.…”