Biological consequences of statins in <i>Candida</i> species and possible implications for human health

Wikhe, K.; Westermeyer, Christiane; Macreadie, Ian

doi:10.1042/bst0351529

Cited by 29 publications

(20 citation statements)

References 42 publications

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“…9, 12, 13 We established that at the concentration of statin and for the period of treatment we employed, petite formation did not occur (Supplementary Fig. 1).…”

Section: Resultsmentioning

confidence: 88%

Suppression of statin effectiveness by copper and zinc in yeast and human cells

et al. 2011

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Summary Lovastatin and other statins inhibit HMG-CoA reductase, which carries out an early step in the sterol biosynthesis pathway. Statins lower cholesterol and are widely prescribed to prevent heart disease, but like many drugs, they can interact with nutritionally acquired metabolites. To probe these interactions, we explored the effect of a diverse library of metabolites on statin effectiveness using a Saccharomyces cerevisiae model. In yeast, treatment with lovastatin results in reduced growth. We combined lovastatin with the library of metabolites, and found that copper and zinc ions impaired the ability of the statin to inhibit yeast growth. Using an integrated genomic and metabolomic approach, we found that lovastatin plus metal synergistically upregulated some sterol biosynthesis genes. This altered pattern of gene expression resulted in greater flux through the sterol biosynthesis pathway and an increase in ergosterol levels. Each sterol intermediate level was correlated with expression of the upstream gene. Thus, the ergosterol biosynthetic response induced by statin is enhanced by copper and zinc. In cultured mammalian cells, these metals also rescued statin growth inhibition. Because copper and zinc impair the ability of statin to reduce sterol biosynthesis, dietary intake of these metals could have clinical relevance for statin treatment in humans.

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“…9, 12, 13 We established that at the concentration of statin and for the period of treatment we employed, petite formation did not occur (Supplementary Fig. 1).…”

Section: Resultsmentioning

confidence: 88%

Suppression of statin effectiveness by copper and zinc in yeast and human cells

et al. 2011

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“…In-vitro studies have demonstrated that simvastatin greatly inhibits the growth of Candida species [15,16]. We performed a review to determine if there was a clinical benefit of statin therapy throughout antifungal therapy in intensive care unit patients with confirmed candidemia.…”

Section: Introductionmentioning

confidence: 99%

Statins in Candidemia: clinical outcomes from a matched cohort study

Forrest

Kopack²,

Perencevich

2010

BMC Infect Dis

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BackgroundHMG CoA reductase inhibitors (statins) in patients with bacteremic sepsis have shown significant survival benefits in several studies. There is no data on the effect of statins in candidemic patients, however in-vitro models suggest that statins interfere with ergesterol formation in the wall of yeasts.MethodsThis retrospective matched- cohort study from 1/2003 to 12/2006 evaluated the effects of statins on patients with candidemia within intensive care units. Statin-users had candidemia as a cause of their systemic inflammatory response and were on statins throughout their antifungal therapy, while non-statin users were matched based on age +/- 5 years and co-morbid factors. Primary analysis was 30-day survival or discharge using bivariable comparisons. Multivariable comparisons were completed using conditional logistic regression. All variables with a p-value less than 0.10 in the bivariable comparisons were considered for inclusion in the conditional logistic model.ResultsThere were 15 statin-users and 30 non-statin users that met inclusion criteria, all with similar demographics and co-morbid conditions except the statin group had more coronary artery disease (P < 0.01) and peripheral vascular disease (P = 0.03) and lower median APCAHE II scores (14.6 vs 17, p = 0.03). There were no differences in duration of candidemia, antifungal therapy or Candida species between the groups. Statins were associated with lower mortality on bivariable (OR 0.09, 95% CI 0.11-0.75, p = 0.03) and multivariable (OR 0.22, 95% CI 0.02-2.4, p = 0.21) analyses compared to controls; although, in the latter the protective effect lacked statistical signficance.ConclusionIn our small, single-center matched-cohort study, statins may provide a survival benefit in candidemia, however further studies are warranted to validate and further explore this association.

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“…In vitro studies have demonstrated that simvastatin inhibits the growth of species of Candida spp. and may be useful in the treatment of candidemias 3,7,12 .…”

Section: Introductionmentioning

confidence: 99%

In vitro synergism of simvastatin and fluconazole against Candida species

Menezes

Júnior

Silva

et al. 2012

Rev. Inst. Med. trop. S. Paulo

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SUMMARYSystemic fungal infections are responsible for high mortality rates. Several species of fungi may be involved, but Candida spp. is the most prevalent. Simvastatin is used to lower cholesterol and also exhibits antifungal action. The aim of this study was to evaluate the synergistic action of simvastatin with fluconazole against strains of Candida spp. Susceptibility testing was performed according to protocol M27-A3, by broth microdilution method and the synergistic effect of simvastatin and fluconazole was calculated based on FICI (Fractional Inhibitory Concentration Index). Eleven strains were evaluated, and simvastatin showed a synergistic effect with fluconazole against 10 (91%) of the Candida spp. strains tested. Simvastatin may be a valuable drug in the treatment of systemic infections caused by Candida spp.

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Biological consequences of statins in Candida species and possible implications for human health

Cited by 29 publications

References 42 publications

Suppression of statin effectiveness by copper and zinc in yeast and human cells

Suppression of statin effectiveness by copper and zinc in yeast and human cells

Statins in Candidemia: clinical outcomes from a matched cohort study

In vitro synergism of simvastatin and fluconazole against Candida species

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