Lovastatin possesses a fungistatic effect against<i>Candida albicans</i>, but does not trigger apoptosis in this opportunistic human pathogen

Gyetvai, Ágnes; Emri, Tamás; Takács, Krisztina; Dergez, Timea; Fekete, Andrea; Pesti, Miklós; Pócsi, István; Lenkey, Béla

doi:10.1111/j.1567-1364.2006.00097.x

Cited by 49 publications

(49 citation statements)

References 47 publications

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“…An inhibitor of squalene synthetase, an intermediate step in the cholesterol pathway, blocked staphyloxanthin production and attendant virulence in Staphylococcus aureus (43). Lovastatin-mediated growth inhibition has been reported for several pathogenic and nonpathogenic yeasts and one mold (31,39,44). For example, 100 M simvastatin or atorvastatin inhibited growth of four Candida species (C. albicans, tropicalis, glabrata, and parapsilosis) as well as Aspergillus fumigatus (36).…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits Candida albicans Biofilm In Vitro

et al. 2009

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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)

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Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits Candida albicans Biofilm In Vitro

et al. 2009

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“…Development and characterization of t BOOH-tolerant C. albicans mutants A series of C. albicans clinical isolates, namely strains 4774 (sex: woman, age: 42 y, diagnosis: cardiorespiratory insufficiency, sample: urine), 8387 (sex: woman, age: 10 y, diagnosis: Langerhans cell histocytolysis, sample: oral cavity), 10934 (sex: woman, age: 45 y, diagnosis: rectal cancer, sample: cannula), 19890 (sex: woman, age: 59 y, diagnosis: thrombotic thrombocytopenic purpura, sample: tissue lesion) and 20072 (sex: man, age: 34 y, diagnosis: pancreatitis, sample: abdominal cavity drainage) randomly selected from the Strain Collection of the Department of Medical Microbiology of the University of Debrecen, was maintained on Sabouraud dextrose agar (SDA) and grown in Sabouraud dextrose broth (SDB) [8,11,12]. As described elsewhere for the tBOOH-tolerant C. albicans AF06 mutant [8], the strains were exposed to stepwise increasing concentrations of tBOOH (2 → 8 mmol l -1 ) in SDB, and the tBOOH-tolerant 4774T, 8387T, 10934T, 19890T and 20072T mutants were randomly chosen for further morphological and physiological studies [8].…”

Section: Methodsmentioning

confidence: 99%

“…Growth kinetics were also recorded in SDB by growing the strains in 100 ml shake flasks (V culture = 20 ml, pH 5.6, 28 °C, 140 rpm, starting OD 640 = 0.1) and monitoring OD 640 values spectrophotometrically for 25 h [8,11,12].…”

Section: Methodsmentioning

confidence: 99%

Physiological and morphological characterization of tert ‐butylhydroperoxide tolerant Candida albicans mutants

Fekete

Pócsi

Emri

et al. 2008

J. Basic Microbiol.

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tert -Butylhydroperoxide (t BOOH) tolerant Candida albicans mutants developed from clinical isolates were characterized with increased tolerance of the oxidative stress generating agents t BOOH and H2O2, continuous induction of the antioxidative defence system, reduced pseudohypha and hypha-forming capabilities, decreased phospholipase secretion and delayed growth in Sabouraud dextrose agar and broth media. Changes in antimycotic (fluconazole, voriconazole, amphotericin B, 5-fluorocytosine) tolerances as well as in total and cytochrome c-dependent respirations showed versatile patterns, meanwhile the intensified alternative oxidase-dependent respiration of the mutants indicated that this respiratory pathway was an important element of the antioxidative defence in general. Because the phenotypes of increased oxidative stress tolerance and reduced virulence attribute production always emerged concomitantly in t BOOH-tolerant mutants the natural selection of C. albicans strains more tolerant of oxidative stress is unlikely. Not surprisingly, a screening study failed to detect any C. albicans strains with increased oxidative stress tolerance among 46 randomly selected clinical isolates.

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“…The MIC determinations vary between different laboratories but are generally in the micromolar range (lowest is 0.4 mg/ml or 0.9 mmol/l). The synergistic effect of statins together with different standard antifungal drugs has also been evaluated [30][31][32][33][34][35][36][37][38][39], and the MIC is then generally lowered, sometimes by as much as with a factor of 10. Two articles report on potent synergistic effects of statins in combination with the atypical drugs primycin [40] and suramin [41] against various moulds.…”

Section: The Clinical Problem: Fungal Infectionsmentioning

confidence: 99%

“…Notably, several of the in vitro studies reported no significant effect of statins against Candida albicans or Aspergillus spp. [33,35,42], whereas others report impaired growth of C. albicans [42], inhibition of C. albicans biofilm [43] and effects on mitochondrial DNA [44]. A recent study shows that several statins exhibit effect against dermatophytes, that is, fungal species causing skin infections [45].…”

Section: The Clinical Problem: Fungal Infectionsmentioning

confidence: 99%

Is there a role for statins in fungal infections?

Bergman

Björkhem‐Bergman

2013

Expert Review of Anti-infective Therapy

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It has been hypothesized that statins, HMG-CoA reductase inhibitors, may be used to treat fungal infections. Here we review data on antifungal properties of statins, effects on the host inflammatory response as well as available clinical evidence. We conclude that: statins exhibit antifungal properties in vitro although at supraphysiological concentrations; statins appear to have anti-inflammatory effects on host cells in vitro; statins have effects on fungal physiology beyond direct growth inhibition; clinical studies are scarce (n = 5), and their design is retrospective and observational, which is associated with a high risk of bias. Given the limited evidence for a beneficial effect of statins in fungal infection, randomized and controlled trials are highly warranted in this field.

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Lovastatin possesses a fungistatic effect againstCandida albicans, but does not trigger apoptosis in this opportunistic human pathogen

Cited by 49 publications

References 47 publications

Simvastatin Inhibits Candida albicans Biofilm In Vitro

Simvastatin Inhibits Candida albicans Biofilm In Vitro

Physiological and morphological characterization of tert ‐butylhydroperoxide tolerant Candida albicans mutants

Is there a role for statins in fungal infections?

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