Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i>
Antifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, <i>Candida auris</i> stands out for commonly...
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MDPI AG
2022-09-01
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| Series: | Journal of Fungi |
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| Online Access: | https://www.mdpi.com/2309-608X/8/10/990 |
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| author | Rafaela F. Amatuzzi Daniel Zamith-Miranda Isadora F. Munhoz da Rocha Aline C. R. Lucena Sharon de Toledo Martins Rodrigo Streit Charley C. Staats Gabriel Trentin Fausto Almeida Marcio L. Rodrigues Joshua D. Nosanchuk Lysangela R. Alves |
| author_facet | Rafaela F. Amatuzzi Daniel Zamith-Miranda Isadora F. Munhoz da Rocha Aline C. R. Lucena Sharon de Toledo Martins Rodrigo Streit Charley C. Staats Gabriel Trentin Fausto Almeida Marcio L. Rodrigues Joshua D. Nosanchuk Lysangela R. Alves |
| author_sort | Rafaela F. Amatuzzi |
| collection | DOAJ |
| description | Antifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, <i>Candida auris</i> stands out for commonly being highly resistant to antifungal drugs, and some isolates are pan-resistant. The rate of mortality linked to <i>C. auris</i> infections varies from 28% to 78%. In this study, we characterized <i>C. auris</i> extracellular vesicles (EVs) in the presence of caspofungin, an echinocandin, which is the recommended first line antifungal for the treatment of infections due to this emerging pathogen. Furthermore, we also analyzed the protein and RNA content of EVs generated by <i>C. auris</i> cultivated with or without treatment with caspofungin. We observed that caspofungin led to the increased production of EVs, and treatment also altered the type and quantity of RNA molecules and proteins enclosed in the EVs. There were distinct classes of RNAs in the EVs with ncRNAs being the most identified molecules, and tRNA-fragments (tRFs) were abundant in each of the strains studied. We also identified anti-sense RNAs, varying from 21 to 55 nt in length. The differentially abundant mRNAs detected in EVs isolated from yeast subjected to caspofungin treatment were related to translation, nucleosome core and cell wall. The differentially regulated proteins identified in the EVs produced during caspofungin treatment were consistent with the results observed with the RNAs, with the enriched terms being related to translation and cell wall. Our study adds new information on how an echinocandin can affect the EV pathway, which is associated with the yeast cell being able to evade treatment and persist in the host. The ability of <i>C. auris</i> to efficiently alter the composition of EVs may represent a mechanism for the fungus to mitigate the effects of antifungal agents. |
| first_indexed | 2024-03-09T20:00:02Z |
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| id | doaj.art-702d7a27d2f04ea2a28bba9e6c246511 |
| institution | Directory Open Access Journal |
| issn | 2309-608X |
| language | English |
| last_indexed | 2024-03-09T20:00:02Z |
| publishDate | 2022-09-01 |
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| series | Journal of Fungi |
| spelling | doaj.art-702d7a27d2f04ea2a28bba9e6c2465112023-11-24T00:46:21ZengMDPI AGJournal of Fungi2309-608X2022-09-0181099010.3390/jof8100990Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i>Rafaela F. Amatuzzi0Daniel Zamith-Miranda1Isadora F. Munhoz da Rocha2Aline C. R. Lucena3Sharon de Toledo Martins4Rodrigo Streit5Charley C. Staats6Gabriel Trentin7Fausto Almeida8Marcio L. Rodrigues9Joshua D. Nosanchuk10Lysangela R. Alves11Gene Expression Regulation Laboratory, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USAGene Expression Regulation Laboratory, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilLaboratory for Applied Sciences and Technology in Health, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilGene Expression Regulation Laboratory, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre 91509-900, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto 14040-900, BrazilDepartment of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto 14040-900, BrazilGene Expression Regulation Laboratory, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USAGene Expression Regulation Laboratory, Carlos Chagas Institute, FIOCRUZ PR, Curitiba 81350-010, BrazilAntifungal resistance has become more frequent, either due to the emergence of naturally resistant species or the development of mechanisms that lead to resistance in previously susceptible species. Among these fungal species of global threat, <i>Candida auris</i> stands out for commonly being highly resistant to antifungal drugs, and some isolates are pan-resistant. The rate of mortality linked to <i>C. auris</i> infections varies from 28% to 78%. In this study, we characterized <i>C. auris</i> extracellular vesicles (EVs) in the presence of caspofungin, an echinocandin, which is the recommended first line antifungal for the treatment of infections due to this emerging pathogen. Furthermore, we also analyzed the protein and RNA content of EVs generated by <i>C. auris</i> cultivated with or without treatment with caspofungin. We observed that caspofungin led to the increased production of EVs, and treatment also altered the type and quantity of RNA molecules and proteins enclosed in the EVs. There were distinct classes of RNAs in the EVs with ncRNAs being the most identified molecules, and tRNA-fragments (tRFs) were abundant in each of the strains studied. We also identified anti-sense RNAs, varying from 21 to 55 nt in length. The differentially abundant mRNAs detected in EVs isolated from yeast subjected to caspofungin treatment were related to translation, nucleosome core and cell wall. The differentially regulated proteins identified in the EVs produced during caspofungin treatment were consistent with the results observed with the RNAs, with the enriched terms being related to translation and cell wall. Our study adds new information on how an echinocandin can affect the EV pathway, which is associated with the yeast cell being able to evade treatment and persist in the host. The ability of <i>C. auris</i> to efficiently alter the composition of EVs may represent a mechanism for the fungus to mitigate the effects of antifungal agents.https://www.mdpi.com/2309-608X/8/10/990<i>Candida auris</i>extracellular vesiclesRNAproteindrug resistance |
| spellingShingle | Rafaela F. Amatuzzi Daniel Zamith-Miranda Isadora F. Munhoz da Rocha Aline C. R. Lucena Sharon de Toledo Martins Rodrigo Streit Charley C. Staats Gabriel Trentin Fausto Almeida Marcio L. Rodrigues Joshua D. Nosanchuk Lysangela R. Alves Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> Journal of Fungi <i>Candida auris</i> extracellular vesicles RNA protein drug resistance |
| title | Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> |
| title_full | Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> |
| title_fullStr | Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> |
| title_full_unstemmed | Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> |
| title_short | Caspofungin Affects Extracellular Vesicle Production and Cargo in <i>Candida auris</i> |
| title_sort | caspofungin affects extracellular vesicle production and cargo in i candida auris i |
| topic | <i>Candida auris</i> extracellular vesicles RNA protein drug resistance |
| url | https://www.mdpi.com/2309-608X/8/10/990 |
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