Pravastatin inhibits farnesol production in Candida albicans and improves survival in a mouse model of systemic candidiasis
Abstract
Candidemia remains a major cause of morbidity and mortality, especially in immunocompromised patients. A strategy of reducing virulence and virulence factors of Candida spp. is an attractive approach for the treatment of serious infections caused by these yeasts. Recently, farnesol has been reported to be a quorum-sensing autoinducer, as well as a virulence factor of C. albicans. In the present study, we examined the effects of pravastatin, a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor on the in vitro production of farnesol. In addition, the synergistic effects of pravastatin with fluconazole (FLC) were examined in a mouse model of systemic infections. In vitro experiments demonstrated that pravastatin had synergistic activity with FLC as judged by fractional inhibitory concentration index (FICI) and suppression of farnesol production at sub-minimum inhibitory concentrations. Furthermore, significant improvement of survival in systemic infection models was shown with pravastatin supplementation. The survival benefits of pravastatin were correlated with reductions of fungal burden. These data suggest the potential of pravastatin as a supportive therapy against C. albicans infections. Synergistic antifungal activity and suppression of HMG-CoA reductase-associated Candida virulence factors, including farnesol, may explain, at least in part, the in vivo efficacy of pravastatin.
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Previous studies suggested that lovastatin and pravastatin disrupted mitochondrial function due to media with glucose as a carbon source, with minor growth inhibition, and that inhibition is significantly enhanced in media with ethanol as the carbon source.
“Previous studies suggested that lovastatin and pravastatin disrupted mitochondrial function due to media with glucose as a carbon source, which exhibited minor growth inhibition. The inhibition is significantly enhanced in media with ethanol as the carbon source [78,79].”
From Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species (2024) · cites this paper as [79]
Pravastatin enhanced survival and led to a decreased fungal burden in C3H/HeN mice infected with C. albicans.
“other work has demonstrated that pravastatin enhanced survival and led to a decreased fungal burden in C3H/HeN mice infected with C. albicans and the potential benefits of statins in the clinic against Candida have been described [10, 40-42].”
From Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans. (2019) · cites this paper as [40]
The azole chemosensitizing activity of statins has been attributed to their ability to interfere with fungal ergosterol biosynthesis.
“Notably, the azole chemosensitizing activity of statins has been attributed to their ability to interfere with the fungal ergosterol biosynthesis26,47.”
From Repurposing approach identifies pitavastatin as a potent azole chemosensitizing agent effective against azole-resistant Candida species (2020) · cites this paper as [47]
Some studies have described potential benefits for statin use during Candida infection in mice and in a clinical setting.
“Although some studies have described potential benefits for statin use during a Candida infection both in mice (Tashiro et al., 2012) and in a clinical setting (Forrest et al., 2010; Spanakis et al., 2010; Cuervo et al., 2013)”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Tashiro et al., 2012
Pravastatin enhances the survival of C. albicans-challenged mice.
“pravastatin has been shown to enhance the survival of C. albicans- challenged mice (Tashiro et al., 2012).”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Tashiro et al., 2012
Tashiro et al. reported enhanced survival and decreased fungal burden in C3H/HeN mice infected with C. albicans treated with pravastatin.
“The study by Tashiro et al. (2012), indicated above, reported enhanced survival and a decreased fungal burden in C3H/HeN mice infected with C. albicans treated with pravastatin.”
From Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice (2015) · cites this paper as Tashiro et al., 2012
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References 30 · Cited by 36
- Authors
- Tashiro, M., Kimura, S., Tateda, K., Saga, T., Ohno, A., Ishii, Y., Izumikawa, K., Tashiro, T., Kohno, S., & Yamaguchi, K.
- Affiliations
- Toho University (JP)
- Nagasaki University (JP)
- Venue
- Medical Mycology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05
- Volume
- 50
- Issue
- 4
- Pages
- 353-360
- ISSN
- 0268-1218 (ISSN-L)
- 1369-3786
- 1460-2709
- OpenAlex
- W2162328944
- Semantic Scholar
- 214336c958830eac53e587f558a38b8f2f83f034
- Cited by
- 36
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2013: 3 · 2012: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Medical Mycology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- pravastatin, Candida albicans, farnesol, quorum sensing, statins, fluconazole, drug synergy, candidemia, systemic candidiasis, antifungal therapy, fungal virulence factors, immunocompromised patients
- MeSH terms
- Animals, Antifungal Agents, Candida albicans, Candidiasis, Disease Models, Animal, Farnesol, Female, Mice, Inbred C3H, Colony Count, Microbial, Survival Analysis, Pravastatin, Virulence Factors, Mice
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