Sub-minimum inhibitory concentrations of statins attenuate the virulence of Rhizopus oryzae. - Université de Tours Accéder directement au contenu
Article Dans Une Revue Journal of Infectious Diseases Année : 2016

Sub-minimum inhibitory concentrations of statins attenuate the virulence of Rhizopus oryzae.

Résumé

 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.  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.  All statins had MICs above 64 µg/mL against R. oryzae. Exposure of R. oryzae to statins decreased germling formation, induced DNA fragmentation, attenuated damage to endothelial cells independently of the expression of GRP78 and CotH. Additionally, R. oryzae exposed to lovastatin showed macroscopic loss of melanin, increased susceptibility to the oxidative agent peroxide and had attenuated virulence in both fly and mouse models of mucormycosis.  Exposure of R. oryzae to statins at sub-MIC concentrations 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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Dates et versions

hal-01294664 , version 1 (29-03-2016)

Identifiants

  • HAL Id : hal-01294664 , version 1
  • PUBMED : 26984141

Citer

Anne-Pauline Bellanger, Fazal Shirazi, Teclegiorgis Gebremariam, Alexander M Tatara, Nathan D Albert, et al.. Sub-minimum inhibitory concentrations of statins attenuate the virulence of Rhizopus oryzae.. Journal of Infectious Diseases, 2016, 94 (1), pp.E17-20. ⟨hal-01294664⟩
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