International Journal of Molecular Sciences (Dec 2022)

Sphingosine as a New Antifungal Agent against <i>Candida</i> and <i>Aspergillus</i> spp.

  • Fahimeh Hashemi Arani,
  • Stephanie Kadow,
  • Melanie Kramer,
  • Simone Keitsch,
  • Lisa Kirchhoff,
  • Fabian Schumacher,
  • Burkhard Kleuser,
  • Peter-Michael Rath,
  • Erich Gulbins,
  • Alexander Carpinteiro

DOI
https://doi.org/10.3390/ijms232415510
Journal volume & issue
Vol. 23, no. 24
p. 15510

Abstract

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This study investigated whether sphingosine is effective as prophylaxis against Aspergillus spp. and Candida spp. In vitro experiments showed that sphingosine is very efficacious against A. fumigatus and Nakeomyces glabrataa (formerly named C. glabrata). A mouse model of invasive aspergillosis showed that sphingosine exerts a prophylactic effect and that sphingosine-treated animals exhibit a strong survival advantage after infection. Furthermore, mechanistic studies showed that treatment with sphingosine leads to the early depolarization of the mitochondrial membrane potential (Δψm) and the generation of mitochondrial reactive oxygen species and to a release of cytochrome C within minutes, thereby presumably initiating apoptosis. Because of its very good tolerability and ease of application, inhaled sphingosine should be further developed as a possible prophylactic agent against pulmonary aspergillosis among severely immunocompromised patients.

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