Is there a role for statins in fungal infections?

Bergman, Peter; Björkhem‐Bergman, Linda

doi:10.1586/14787210.2014.856755

Cited by 11 publications

(20 citation statements)

References 61 publications

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“…The first compound, the HMG-CoA reductase inhibitor simvastatin, is a cholesterol-lowering drug for which antifungal activity has been described previously 44 . Both statins and azoles target the ergosterol biosynthesis pathway in C. albicans .…”

Section: Discussionmentioning

confidence: 99%

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Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

Cremer

Brucker

Staes

et al. 2016

Sci Rep

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We performed a whole-transcriptome analysis of miconazole-treated Candida albicans biofilms, using RNA-sequencing. Our aim was to identify molecular pathways employed by biofilm cells of this pathogen to resist action of the commonly used antifungal miconazole. As expected, genes involved in sterol biosynthesis and genes encoding drug efflux pumps were highly induced in biofilm cells upon miconazole treatment. Other processes were affected as well, including the electron transport chain (ETC), of which eight components were transcriptionally downregulated. Within a diverse set of 17 inhibitors/inducers of the transcriptionally affected pathways, the ETC inhibitors acted most synergistically with miconazole against C. albicans biofilm cells. Synergy was not observed for planktonically growing C. albicans cultures or when biofilms were treated in oxygen-deprived conditions, pointing to a biofilm-specific oxygen-dependent tolerance mechanism. In line, a correlation between miconazole’s fungicidal action against C. albicans biofilm cells and the levels of superoxide radicals was observed, and confirmed both genetically and pharmacologically using a triple superoxide dismutase mutant and a superoxide dismutase inhibitor N-N′-diethyldithiocarbamate, respectively. Consequently, ETC inhibitors that result in mitochondrial dysfunction and affect production of reactive oxygen species can increase miconazole’s fungicidal activity against C. albicans biofilm cells.

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Section: Discussionmentioning

confidence: 99%

“…The potential of statins in systemic antifungal therapy is debated, due to the low concentrations that can be reached in blood. Moreover, the combination of statins with azole antifungals is questionable since azoles are potent inhibitors of CYP enzymes, leading to arrested metabolism of many statins in the liver 44 .…”

Section: Discussionmentioning

confidence: 99%

Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

Cremer

Brucker

Staes

et al. 2016

Sci Rep

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“…Regarding the medication of these patients, several molecules are reported to be associated with altered susceptibility to fungal infections and can influence yeast colonization in this population. 47.6% of the PD patients were on calcium channel blockers therapy, described to have an inhibitory effect on oxidative stress response of Candida albicans [ 11 ]; 57.1% were prescribed with statins, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, used to lower patients' cholesterol but that also affects ergosterol levels exhibiting antifungal properties [ 12 ]; 71.4% were supplemented with vitamin D known to affect fungal growth in a dose-dependent manner [ 13 ]; and 90.5% had iron supplementation, an essential element for microbial growth and known to influence host susceptibility to C. albicans infections [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study

Simões-Silva

Silva

Santos-Araújo

et al. 2017

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Peritonitis and exit-site infections are important complications in peritoneal dialysis (PD) patients that are occasionally caused by opportunistic fungi inhabiting distant body sites. In this study, the oral yeast colonization of PD patients and the antifungal susceptibility profile of the isolated yeasts were accessed and correlated with fungal infection episodes in the following 4 years. Saliva yeast colonization was accessed in 21 PD patients and 27 healthy controls by growth in CHROMagar-Candida® and 18S rRNA/ITS sequencing. PD patients presented a lower oral yeast prevalence when compared to controls, namely, Candida albicans. Other species were also isolated, Candida glabrata and Candida carpophila. The antifungal susceptibility profiles of these isolates revealed resistance to itraconazole, variable susceptibility to caspofungin, and higher MIC values of posaconazole compared to previous reports. The 4-year longitudinal evaluation of these patients revealed Candida parapsilosis and Candida zeylanoides as PD-related exit-site infectious agents, but no correlation was found with oral yeast colonization. This pilot study suggests that oral yeast colonization may represent a limited risk for fungal infection development in PD patients. Oral yeast isolates presented a variable antifungal susceptibility profile, which may suggest resistance to some second-line drugs, highlighting the importance of antifungal susceptibility assessment in the clinical practice.

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“…HMG-CoA inhibitors, a class known as statins, are widely used in humans to reduce cholesterol levels. The similarity between human and fungal HMG-CoA has raised interest in the potential of statins as antifungal drugs (Bergman and Björkhem-Bergman, 2013). However a meta analysis of five retrospective studies found no positive effects for the use of statins during fungal infection (Bergman and Björkhem-Bergman, 2013).…”

Section: Hmg-coa Reductase Inhibitorsmentioning

confidence: 99%

Cryptococcal therapies and drug targets: the old, the new and the promising

Coelho

Casadevall

2016

Cellular Microbiology

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Summary Half a century after the introduction of Amphotericin B the management of cryptococcosis remains unsatisfactory. The disease, caused primarily by the two fungal species Cryptococcus neoformans and Cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. Current therapeutic options are limited to Amphotericin B, azoles and 5-flucytosine. However, this organism has numerous well-characterized virulence mechanisms that are amenable to pharmacological interference and are thus potential therapeutic targets. Here, we discuss existing approved antifungal drugs, resistance mechanisms to these drugs and non-standard antifungal drugs that have potential in treatment of cryptococcosis, including immunomodulatory strategies that synergize with antifungal drugs, such as cytokine administration or monoclonal antibodies. Finally, we summarize attempts to target well-described virulence factors of Cryptococcus, the capsule or fungal melanin. This review emphasizes the pressing need for new therapeutic alternatives for cryptococcosis.

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Is there a role for statins in fungal infections?

Cited by 11 publications

References 61 publications

Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms

Oral Yeast Colonization and Fungal Infections in Peritoneal Dialysis Patients: A Pilot Study

Cryptococcal therapies and drug targets: the old, the new and the promising

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