Journal of Fungi (Dec 2023)

Miltefosine: A Repurposing Drug against Mucorales Pathogens

  • Mariana Ingrid Dutra da Silva Xisto,
  • Rodrigo Rollin-Pinheiro,
  • Victor Pereira Rochetti,
  • Yuri de Castro-Almeida,
  • Luana Pereira Borba-Santos,
  • Giulia Maria Pires dos Santos-Freitas,
  • Jefferson Cypriano,
  • Fernanda de Ávila Abreu,
  • Sonia Rozental,
  • Eliana Barreto-Bergter

DOI
https://doi.org/10.3390/jof9121166
Journal volume & issue
Vol. 9, no. 12
p. 1166

Abstract

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Mucorales are a group of non-septated filamentous fungi widely distributed in nature, frequently associated with human infections, and are intrinsically resistant to many antifungal drugs. For these reasons, there is an urgent need to improve the clinical management of mucormycosis. Miltefosine, which is a phospholipid analogue of alkylphosphocholine, has been considered a promising repurposing drug to be used to treat fungal infections. In the present study, miltefosine displayed antifungal activity against a variety of Mucorales species, and it was also active against biofilms formed by these fungi. Treatment with miltefosine revealed modifications of cell wall components, neutral lipids, mitochondrial membrane potential, cell morphology, and the induction of oxidative stress. Treated Mucorales cells also presented an increased susceptibility to SDS. Purified ergosterol and glucosylceramide added to the culture medium increased miltefosine MIC, suggesting its interaction with fungal lipids. These data contribute to elucidating the effect of a promising drug repurposed to act against some relevant fungal pathogens that significantly impact public health.

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