Miltefosine: A Repurposing Drug against Mucorales Pathogens
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, whi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/12/1166 |
| _version_ | 1797380412870230016 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Mariana Ingrid Dutra da Silva Xisto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T20:36:53Z |
| format | Article |
| id | doaj.art-76cdb82b60214b9d820048a0090d388c |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-08T20:36:53Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-76cdb82b60214b9d820048a0090d388c2023-12-22T14:19:22ZengMDPI AGJournal of Fungi2309-608X2023-12-01912116610.3390/jof9121166Miltefosine: A Repurposing Drug against Mucorales PathogensMariana Ingrid Dutra da Silva Xisto0Rodrigo Rollin-Pinheiro1Victor Pereira Rochetti2Yuri de Castro-Almeida3Luana Pereira Borba-Santos4Giulia Maria Pires dos Santos-Freitas5Jefferson Cypriano6Fernanda de Ávila Abreu7Sonia Rozental8Eliana Barreto-Bergter9Laboratório 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, BrazilLaboratório 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, BrazilLaboratório 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, BrazilLaboratório 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, BrazilLaboratório de Biologia Celular de Fungos, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório 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, BrazilLaboratório de Biologia Celular e Magnetotaxia & Unidade de Microscopia Multiusuário, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biologia Celular e Magnetotaxia & Unidade de Microscopia Multiusuário, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório de Biologia Celular de Fungos, Programa de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, BrazilLaboratório 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, BrazilMucorales 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.https://www.mdpi.com/2309-608X/9/12/1166miltefosineMucorales<i>Rhizopus oryzae</i><i>Rhizopus stolonifer</i><i>Rhizopus microsporus</i><i>Cunninghamella</i> spp. |
| spellingShingle | 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 Miltefosine: A Repurposing Drug against Mucorales Pathogens Journal of Fungi miltefosine Mucorales <i>Rhizopus oryzae</i> <i>Rhizopus stolonifer</i> <i>Rhizopus microsporus</i> <i>Cunninghamella</i> spp. |
| title | Miltefosine: A Repurposing Drug against Mucorales Pathogens |
| title_full | Miltefosine: A Repurposing Drug against Mucorales Pathogens |
| title_fullStr | Miltefosine: A Repurposing Drug against Mucorales Pathogens |
| title_full_unstemmed | Miltefosine: A Repurposing Drug against Mucorales Pathogens |
| title_short | Miltefosine: A Repurposing Drug against Mucorales Pathogens |
| title_sort | miltefosine a repurposing drug against mucorales pathogens |
| topic | miltefosine Mucorales <i>Rhizopus oryzae</i> <i>Rhizopus stolonifer</i> <i>Rhizopus microsporus</i> <i>Cunninghamella</i> spp. |
| url | https://www.mdpi.com/2309-608X/9/12/1166 |
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