Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp.
<i>Candida</i> species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive <i>Candida</i> infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/9/11/1115 |
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| author | Rodrigo Rollin-Pinheiro Daniel Clemente de Moraes Brayan Bayona-Pacheco Jose Alexandre da Rocha Curvelo Giulia Maria Pires dos Santos-Freitas Mariana Ingrid Dutra da Silva Xisto Luana Pereira Borba-Santos Sonia Rozental Antonio Ferreira-Pereira Eliana Barreto-Bergter |
| author_facet | Rodrigo Rollin-Pinheiro Daniel Clemente de Moraes Brayan Bayona-Pacheco Jose Alexandre da Rocha Curvelo Giulia Maria Pires dos Santos-Freitas Mariana Ingrid Dutra da Silva Xisto Luana Pereira Borba-Santos Sonia Rozental Antonio Ferreira-Pereira Eliana Barreto-Bergter |
| author_sort | Rodrigo Rollin-Pinheiro |
| collection | DOAJ |
| description | <i>Candida</i> species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive <i>Candida</i> infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity. Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the sphingolipid biosynthetic pathway have been described to display antifungal properties, such as myriocin and aureobasidin A, which are active against resistant <i>Candida</i> isolates. In the present study, aureobasidin A did not display antibiofilm activity nor synergism with amphotericin B, but its combination with fluconazole was effective against <i>Candida</i> biofilms and protected the host in an in vivo infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and chitin content, as well as altered morphology, enhanced DNA leakage and a greater susceptibility to sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of <i>Candida</i> species. |
| first_indexed | 2024-03-09T16:41:24Z |
| format | Article |
| id | doaj.art-baf6d6a917a9462c9c2b637d27cf1013 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T16:41:24Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Fungi |
| spelling | doaj.art-baf6d6a917a9462c9c2b637d27cf10132023-11-24T14:51:12ZengMDPI AGJournal of Fungi2309-608X2023-11-01911111510.3390/jof9111115Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp.Rodrigo Rollin-Pinheiro0Daniel Clemente de Moraes1Brayan Bayona-Pacheco2Jose Alexandre da Rocha Curvelo3Giulia Maria Pires dos Santos-Freitas4Mariana Ingrid Dutra da Silva Xisto5Luana Pereira Borba-Santos6Sonia Rozental7Antonio Ferreira-Pereira8Eliana Barreto-Bergter9Laboratório de Química Biológica de Microrganismos, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), 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 (UFRJ), 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 (UFRJ), Rio de Janeiro 21941-902, BrazilPrograma de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, BrazilPrograma de Biologia Celular e Parasitologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro 21941-902, BrazilLaboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), 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 (UFRJ), Rio de Janeiro 21941-902, Brazil<i>Candida</i> species are one of the most concerning causative agents of fungal infections in humans. The treatment of invasive <i>Candida</i> infections is based on the use of fluconazole, but the emergence of resistant isolates has been an increasing concern which has led to the study of alternative drugs with antifungal activity. Sphingolipids have been considered a promising target due to their roles in fungal growth and virulence. Inhibitors of the sphingolipid biosynthetic pathway have been described to display antifungal properties, such as myriocin and aureobasidin A, which are active against resistant <i>Candida</i> isolates. In the present study, aureobasidin A did not display antibiofilm activity nor synergism with amphotericin B, but its combination with fluconazole was effective against <i>Candida</i> biofilms and protected the host in an in vivo infection model. Alterations in treated cells revealed increased oxidative stress, reduced mitochondrial membrane potential and chitin content, as well as altered morphology, enhanced DNA leakage and a greater susceptibility to sodium dodecyl sulphate (SDS). In addition, it seems to inhibit the efflux pump CaCdr2p. All these data contribute to elucidating the role of aureobasidin A on fungal cells, especially evidencing its promising use in clinical resistant isolates of <i>Candida</i> species.https://www.mdpi.com/2309-608X/9/11/1115aureobasidin Asphingolipids<i>Candida</i>membranefungal infection |
| spellingShingle | Rodrigo Rollin-Pinheiro Daniel Clemente de Moraes Brayan Bayona-Pacheco Jose Alexandre da Rocha Curvelo Giulia Maria Pires dos Santos-Freitas Mariana Ingrid Dutra da Silva Xisto Luana Pereira Borba-Santos Sonia Rozental Antonio Ferreira-Pereira Eliana Barreto-Bergter Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. Journal of Fungi aureobasidin A sphingolipids <i>Candida</i> membrane fungal infection |
| title | Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. |
| title_full | Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. |
| title_fullStr | Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. |
| title_full_unstemmed | Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. |
| title_short | Structural and Functional Alterations Caused by Aureobasidin A in Clinical Resistant Strains of <i>Candida</i> spp. |
| title_sort | structural and functional alterations caused by aureobasidin a in clinical resistant strains of i candida i spp |
| topic | aureobasidin A sphingolipids <i>Candida</i> membrane fungal infection |
| url | https://www.mdpi.com/2309-608X/9/11/1115 |
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