Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence of Rhizopus oryzae
Open accessAbstract
BACKGROUND: Mucormycosis is a destructive invasive mold infection afflicting patients with diabetes and hematologic malignancies. Patients with diabetes are often treated with statins, which have been shown to have antifungal properties. We sought to examine the effects of statins on Rhizopus oryzae, a common cause of mucormycosis. METHODS: Clinical strains of R. oryzae were exposed to lovastatin, atorvastatin, and simvastatin and the minimum inhibitory concentrations (MICs) were determined. R. oryzae germination, DNA fragmentation, susceptibility to oxidative stress, and ability to damage endothelial cells were assessed. We further investigated the impact of exposure to lovastatin on the virulence of R. oryzae RESULTS: All statins had MICs of >64 µg/mL against R. oryzae Exposure of R. oryzae to statins decreased germling formation, induced DNA fragmentation, and attenuated damage to endothelial cells independently of the expression of GRP78 and CotH. Additionally, R. oryzae exposed to lovastatin showed macroscopic loss of melanin, yielded increased susceptibility to the oxidative agent peroxide, and had attenuated virulence in both fly and mouse models of mucormycosis. CONCLUSIONS: Exposure of R. oryzae to statins at concentrations below their MICs decreased virulence both in vitro and in vivo. Further investigation is warranted into the use of statins as adjunctive therapy in mucormycosis.
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Exposure to lovastatin results in macroscopic melanin loss and diminished virulence in mucormycosis models using flies and mice.
“They also reported that exposure to lovastatin resulted in macroscopic melanin loss and diminished virulence in mucormycosis models using flies and mice.”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [120]
Lovastatin, atorvastatin, and simvastatin cause DNA fragmentation and reduce spore germination in Rhizopus oryzae.
“Bellanger et al. [120] investigated the effects of lovastatin, atorvastatin, and simvastatin on Rhizopus oryzae and observed DNA fragmentation and a reduction in spore germination.”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [120]
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“Bellanger et al. [120] investigated the effects of lovastatin, ator-vastatin, and simvastatin on Rhizopus oryzae and observed DNA fragmentation and a reduction in spore germination.”
Topical statins as antifungals: a review
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- Authors
- Bellanger, A.-P., Tatara, A. M., Shirazi, F., Gebremariam, T., Albert, N. D., Lewis, R. E., Ibrahim, A. S., & Kontoyiannis, D. P.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- The Lundquist Institute (US)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Corresponding author
- Bellanger, Anne-Pauline
- ORCID
- Venue
- Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-16
- Volume
- 214
- Issue
- 1
- Pages
- 114-121
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC5007635
- OpenAlex
- W2415911582
- Cited by
- 41
- References
- 26
- Citations by year
- 2025: 6 · 2024: 5 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 2 · 2019: 6 · 2018: 4 · 2017: 3
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Public Health Service (R01 AI063503 and 1R41 AI115907-01)
- National Center for Advancing Translational Sciences (UL1TR000124)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- mucormycosis, Rhizopus oryzae, statins, lovastatin, atorvastatin, simvastatin, antifungal activity, fungal virulence, spore germination, DNA fragmentation, oxidative stress, melanin, endothelial injury, adjunctive antifungal therapy, diabetes mellitus
- MeSH terms
- Atorvastatin, Endoplasmic Reticulum Chaperone BiP, Animals, Antifungal Agents, Diptera, Female, Humans, Lovastatin, Microbial Sensitivity Tests, Mucormycosis, Rhizopus, Spores, Fungal, Texas, Virulence, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Mice
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