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Miltefosine: A Repurposing Drug against Mucorales Pathogens.
Mariana Ingrid Dutra da Silva Xisto1, Rodrigo Rollin-Pinheiro1, Victor Pereira Rochetti1
1Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Journal of Fungi (Basel, Switzerland)
|December 22, 2023
Summary
Miltefosine shows antifungal activity against Mucorales, a group of fungi causing infections and resistant to drugs. This study explores its effects on fungal cells and biofilms, offering a potential new treatment for mucormycosis.
Area of Science:
- Mycology
- Infectious Diseases
- Drug Discovery
Background:
- Mucorales are non-septated fungi causing infections and are drug-resistant.
- Mucormycosis management requires improved therapeutic options.
- Miltefosine, a phospholipid analogue, is a potential repurposed antifungal agent.
Purpose of the Study:
- To evaluate the antifungal activity of miltefosine against Mucorales species.
- To investigate the mechanism of action of miltefosine in Mucorales.
- To assess miltefosine's efficacy against Mucorales biofilms.
Main Methods:
- Antifungal susceptibility testing (MIC) against various Mucorales species.
- Biofilm inhibition assays.
- Analysis of cellular changes (cell wall, lipids, mitochondrial potential, morphology, oxidative stress) post-treatment.
- Assessment of synergistic effects with SDS and lipid components.
Main Results:
- Miltefosine demonstrated antifungal activity against Mucorales species and their biofilms.
- Treatment induced alterations in cell wall, neutral lipids, mitochondrial membrane potential, and cell morphology.
- Oxidative stress was induced, and cells showed increased susceptibility to SDS.
- Ergosterol and glucosylceramide partially reversed miltefosine's effect, suggesting lipid interaction.
Conclusions:
- Miltefosine is a promising repurposed drug for treating Mucorales infections.
- The drug affects multiple cellular components and induces oxidative stress.
- Understanding miltefosine's interaction with fungal lipids is key to its therapeutic application.
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