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Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.

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 showe...

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Autores principales: Hashemi Arani, Fahimeh, Kadow, Stephanie, Kramer, Melanie, Keitsch, Simone, Kirchhoff, Lisa, Schumacher, Fabian, Kleuser, Burkhard, Rath, Peter-Michael, Gulbins, Erich, Carpinteiro, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779773/
https://www.ncbi.nlm.nih.gov/pubmed/36555152
http://dx.doi.org/10.3390/ijms232415510
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author Hashemi Arani, Fahimeh
Kadow, Stephanie
Kramer, Melanie
Keitsch, Simone
Kirchhoff, Lisa
Schumacher, Fabian
Kleuser, Burkhard
Rath, Peter-Michael
Gulbins, Erich
Carpinteiro, Alexander
author_facet Hashemi Arani, Fahimeh
Kadow, Stephanie
Kramer, Melanie
Keitsch, Simone
Kirchhoff, Lisa
Schumacher, Fabian
Kleuser, Burkhard
Rath, Peter-Michael
Gulbins, Erich
Carpinteiro, Alexander
author_sort Hashemi Arani, Fahimeh
collection PubMed
description 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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spelling pubmed-97797732022-12-23 Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp. Hashemi Arani, Fahimeh Kadow, Stephanie Kramer, Melanie Keitsch, Simone Kirchhoff, Lisa Schumacher, Fabian Kleuser, Burkhard Rath, Peter-Michael Gulbins, Erich Carpinteiro, Alexander Int J Mol Sci Article 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. MDPI 2022-12-07 /pmc/articles/PMC9779773/ /pubmed/36555152 http://dx.doi.org/10.3390/ijms232415510 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hashemi Arani, Fahimeh
Kadow, Stephanie
Kramer, Melanie
Keitsch, Simone
Kirchhoff, Lisa
Schumacher, Fabian
Kleuser, Burkhard
Rath, Peter-Michael
Gulbins, Erich
Carpinteiro, Alexander
Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title_full Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title_fullStr Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title_full_unstemmed Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title_short Sphingosine as a New Antifungal Agent against Candida and Aspergillus spp.
title_sort sphingosine as a new antifungal agent against candida and aspergillus spp.
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779773/
https://www.ncbi.nlm.nih.gov/pubmed/36555152
http://dx.doi.org/10.3390/ijms232415510
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