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Statin Concentrations Below the Minimum Inhibitory Concentration Attenuate the Virulence of Rhizopus oryzae

Anne-Pauline Bellanger1, Alexander M Tatara1, Fazal Shirazi1

  • 1Department of Infectious Disease, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston.

The Journal of Infectious Diseases
|March 18, 2016
PubMed
Abstract

Insights

Statins show antifungal properties against Rhizopus oryzae, a cause of mucormycosis. Even at low doses, statins reduced fungal virulence in lab and animal models, suggesting potential as an adjunctive therapy.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Mucormycosis is a severe invasive mold infection.
  • Patients with diabetes and hematologic malignancies are particularly vulnerable.
  • Statins, commonly used for diabetes, possess known antifungal properties.

Purpose of the Study:

  • To investigate the effects of statins on Rhizopus oryzae, a primary cause of mucormycosis.
  • To determine if statins can inhibit R. oryzae growth and reduce its virulence.

Main Methods:

  • Determined minimum inhibitory concentrations (MICs) of lovastatin, atorvastatin, and simvastatin against R. oryzae.
  • Assessed R. oryzae germination, DNA fragmentation, and endothelial cell damage.
  • Evaluated the impact of lovastatin on R. oryzae melanin, oxidative stress susceptibility, and virulence in fly and mouse models.

Main Results:

  • Statins exhibited MICs greater than 64 µg/mL against R. oryzae.
  • Statin exposure reduced R. oryzae germling formation and induced DNA fragmentation.
  • Lovastatin exposure led to melanin loss, increased peroxide susceptibility, and attenuated virulence in vivo.

Conclusions:

  • Statins, at sub-MIC concentrations, decreased R. oryzae virulence both in vitro and in vivo.
  • Statins demonstrate potential as an adjunctive therapy for mucormycosis.
Keywords:
Rhizopus oryzaeapoptosisfly modelgerminationmurine modelstatinsvirulence

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