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- Title
Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
- Authors
Hashemi Arani, Fahimeh; Kadow, Stephanie; Kramer, Melanie; Keitsch, Simone; Kirchhoff, Lisa; Schumacher, Fabian; Kleuser, Burkhard; Rath, Peter-Michael; Gulbins, Erich; Carpinteiro, Alexander
- Abstract
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.
- Subjects
SPHINGOSINE; PULMONARY aspergillosis; ASPERGILLUS; ASPERGILLUS fumigatus; REACTIVE oxygen species; ANTIFUNGAL agents
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 24, p15510
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms232415510