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A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi
Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) agains...
| Autores principales: | , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2023
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090755/ https://www.ncbi.nlm.nih.gov/pubmed/37045836 http://dx.doi.org/10.1038/s41467-023-37573-y |
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| author | dos Reis, Thaila Fernanda de Castro, Patrícia Alves Bastos, Rafael Wesley Pinzan, Camila Figueiredo Souza, Pedro F. N. Ackloo, Suzanne Hossain, Mohammad Anwar Drewry, David Harold Alkhazraji, Sondus Ibrahim, Ashraf S. Jo, Hyunil Lightfoot, Jorge D. Adams, Emily M. Fuller, Kevin K. deGrado, William F. Goldman, Gustavo H. |
| author_facet | dos Reis, Thaila Fernanda de Castro, Patrícia Alves Bastos, Rafael Wesley Pinzan, Camila Figueiredo Souza, Pedro F. N. Ackloo, Suzanne Hossain, Mohammad Anwar Drewry, David Harold Alkhazraji, Sondus Ibrahim, Ashraf S. Jo, Hyunil Lightfoot, Jorge D. Adams, Emily M. Fuller, Kevin K. deGrado, William F. Goldman, Gustavo H. |
| author_sort | dos Reis, Thaila Fernanda |
| collection | PubMed |
| description | Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections. |
| format | Online Article Text |
| id | pubmed-10090755 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2023 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-100907552023-04-14 A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi dos Reis, Thaila Fernanda de Castro, Patrícia Alves Bastos, Rafael Wesley Pinzan, Camila Figueiredo Souza, Pedro F. N. Ackloo, Suzanne Hossain, Mohammad Anwar Drewry, David Harold Alkhazraji, Sondus Ibrahim, Ashraf S. Jo, Hyunil Lightfoot, Jorge D. Adams, Emily M. Fuller, Kevin K. deGrado, William F. Goldman, Gustavo H. Nat Commun Article Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as a synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans, C. auris, and CAS-intrinsically resistant Cryptococcus neoformans. BRI also potentiates azoles against A. fumigatus and several Mucorales fungi. BRI acts in A. fumigatus by affecting cell wall integrity pathway and cell membrane potential. BRI combined with CAS significantly clears A. fumigatus lung infection in an immunosuppressed murine model of invasive pulmonary aspergillosis. BRI alone also decreases A. fumigatus fungal burden and ablates disease development in a murine model of fungal keratitis. Our results indicate that combinations of BRI and antifungal drugs in clinical use are likely to improve the treatment outcome of aspergillosis and other fungal infections. Nature Publishing Group UK 2023-04-12 /pmc/articles/PMC10090755/ /pubmed/37045836 http://dx.doi.org/10.1038/s41467-023-37573-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article dos Reis, Thaila Fernanda de Castro, Patrícia Alves Bastos, Rafael Wesley Pinzan, Camila Figueiredo Souza, Pedro F. N. Ackloo, Suzanne Hossain, Mohammad Anwar Drewry, David Harold Alkhazraji, Sondus Ibrahim, Ashraf S. Jo, Hyunil Lightfoot, Jorge D. Adams, Emily M. Fuller, Kevin K. deGrado, William F. Goldman, Gustavo H. A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title | A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title_full | A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title_fullStr | A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title_full_unstemmed | A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title_short | A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| title_sort | host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10090755/ https://www.ncbi.nlm.nih.gov/pubmed/37045836 http://dx.doi.org/10.1038/s41467-023-37573-y |
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