Journal Article

<i>In vitro</i> activity of aminosterols against yeasts involved in blood stream infections

Kamel Alhanout, Lamia Djouhri, Nicolas Vidal, Jean Michel Brunel, Renaud Piarroux and Stéphane Ranque

in Medical Mycology

Published on behalf of International Society for Human and Animal Mycology

Volume 49, issue 2, pages 121-125
Published in print February 2011 | ISSN: 1369-3786
Published online February 2011 | e-ISSN: 1460-2709 | DOI: http://dx.doi.org/10.3109/13693786.2010.502189
In vitro activity of aminosterols against yeasts involved in blood stream infections

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  • Mycology and Fungi
  • Infectious Diseases
  • Medical Toxicology
  • Veterinary Medicine
  • Environmental Science

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Squalamine and other aminosterols have demonstrated interesting antimicrobial activities against clinical bacterial isolates and a limited number of reference yeast strains. We aimed to test whether squalamine and a synthetic aminosterol derivative (ASD) display any in vitro activity comparable to currently available systemic antifungals, an acceptable safety index, as well as to provide insights into their mechanism of action. The minimum inhibitory concentrations (MICs) of squalamine, ASD and available antifungals were determined against 21 yeast isolates that were recovered from cases of fungemia. Remarkably, homogeneous MICs ranging from 8–16 mg/L and from 1–2 mg/L were noted for squalamine and ASD, respectively, as opposes the heterogenous in vitro activity of available systemic antifungals. Aminosterols induced haemolysis, a surrogate for toxic effects to mammalian cells, at concentrations high above their MICs. In time-kill studies, killing was as fast with ASD as with amphotericin B. Both aminosterols induced a time-dependent disruption of yeast membrane, as evidenced by gradual increase of ATP efflux. In conclusion, our preliminary data indicate that aminosterols have the potential to be further developed as antifungals. Additional work is warranted to assess their toxicity and activity in experimental models.

Keywords: squalamine; antifungal; resistance; therapy

Journal Article.  1882 words.  Illustrated.

Subjects: Mycology and Fungi ; Infectious Diseases ; Medical Toxicology ; Veterinary Medicine ; Environmental Science

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