Transcriptional and translational landscape of Candida auris in response to caspofungin
Abstract
Candida auris has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against C. auris. In this work, we treated two distinct strains of C. auris for 24h with caspofungin, and the cellular responses were evaluated at the morphological, translational and transcriptional levels. We first observed that the echinocandin caused morphological alterations, aggregation of yeast cells, and modifications in the cell wall composition of C. auris. Transcriptomic analysis revealed an upregulation of genes related to the synthesis of the cell wall, ribosome, and cell cycle after exposure to caspofungin. Supporting these findings, the integrated proteomic analysis showed that caspofungin-treated cells were enriched in ribosome-related proteins and cell wall, especially mannoproteins. Altogether, these results provide further insights into the biology of C. auris and expands our understanding regardingmore »
- Authors:
-
[1];
[2];
[3];
[4];
[5];
[6];
[1];
[2]
- Albert Einstein College of Medicine, New York, NY (United States)
- Carlos Chagas Inst., Curitiba (Brazil). FIOCRUZ PR, Gene Expression Regulation Lab.
- Carlos Chagas Inst., Curitiba (Brazil). FIOCRUZ PR, Lab. for Applied Sciences and Technology in Health
- Univ. of São Paulo (Brazil)
- Carlos Chagas Inst., Curitiba (Brazil). FIOCRUZ PR, Gene Expression Regulation Lab.; Federal Univ. of Rio de Janeiro (UFRJ) (Brazil), Microbiology Inst.
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Publication Date:
- Research Org.:
- Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
- Sponsoring Org.:
- USDOE; CNPq; National Institutes of Health (NIH); Fiocruz
- OSTI Identifier:
- 1837548
- Report Number(s):
- PNNL-SA-167223
Journal ID: ISSN 2001-0370
- Grant/Contract Number:
- AC05-76RL01830; R21 AI124797; 440015/2018-9; 405520/2018-2; 301304/2017-3; VPPCB-007-FIO-18; VPPIS-001-FIO18; 442317/2019-0
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Computational and Structural Biotechnology Journal
- Additional Journal Information:
- Journal Volume: 19; Journal ID: ISSN 2001-0370
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Candida auris; Transcriptomics; Proteomics; Drug resistance; Stress response
Citation Formats
Zamith-Miranda, Daniel, Amatuzzi, Rafaela F., Munhoz da Rocha, Isadora F., Martins, Sharon T., Lucena, Aline C.R., Vieira, Alexandre Z., Trentin, Gabriel, Almeida, Fausto, Rodrigues, Marcio L., Nakayasu, Ernesto S., Nosanchuk, Joshua D., and Alves, Lysangela R. Transcriptional and translational landscape of Candida auris in response to caspofungin. United States: N. p., 2021.
Web. doi:10.1016/j.csbj.2021.09.007.
Zamith-Miranda, Daniel, Amatuzzi, Rafaela F., Munhoz da Rocha, Isadora F., Martins, Sharon T., Lucena, Aline C.R., Vieira, Alexandre Z., Trentin, Gabriel, Almeida, Fausto, Rodrigues, Marcio L., Nakayasu, Ernesto S., Nosanchuk, Joshua D., & Alves, Lysangela R. Transcriptional and translational landscape of Candida auris in response to caspofungin. United States. https://doi.org/10.1016/j.csbj.2021.09.007
Zamith-Miranda, Daniel, Amatuzzi, Rafaela F., Munhoz da Rocha, Isadora F., Martins, Sharon T., Lucena, Aline C.R., Vieira, Alexandre Z., Trentin, Gabriel, Almeida, Fausto, Rodrigues, Marcio L., Nakayasu, Ernesto S., Nosanchuk, Joshua D., and Alves, Lysangela R. Mon .
"Transcriptional and translational landscape of Candida auris in response to caspofungin". United States. https://doi.org/10.1016/j.csbj.2021.09.007. https://www.osti.gov/servlets/purl/1837548.
@article{osti_1837548,
title = {Transcriptional and translational landscape of Candida auris in response to caspofungin},
author = {Zamith-Miranda, Daniel and Amatuzzi, Rafaela F. and Munhoz da Rocha, Isadora F. and Martins, Sharon T. and Lucena, Aline C.R. and Vieira, Alexandre Z. and Trentin, Gabriel and Almeida, Fausto and Rodrigues, Marcio L. and Nakayasu, Ernesto S. and Nosanchuk, Joshua D. and Alves, Lysangela R.},
abstractNote = {Candida auris has emerged as a serious worldwide threat by causing opportunistic infections that are frequently resistant to one or more conventional antifungal medications resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective prevention and treatment approaches to combat this fungus. To date, there is little information about the differentially expressed genes when this fungus is treated with conventional antifungals, and caspofungin is a standard echinocandin deployed in the therapy against C. auris. In this work, we treated two distinct strains of C. auris for 24h with caspofungin, and the cellular responses were evaluated at the morphological, translational and transcriptional levels. We first observed that the echinocandin caused morphological alterations, aggregation of yeast cells, and modifications in the cell wall composition of C. auris. Transcriptomic analysis revealed an upregulation of genes related to the synthesis of the cell wall, ribosome, and cell cycle after exposure to caspofungin. Supporting these findings, the integrated proteomic analysis showed that caspofungin-treated cells were enriched in ribosome-related proteins and cell wall, especially mannoproteins. Altogether, these results provide further insights into the biology of C. auris and expands our understanding regarding the antifungal activity of caspofungin and reveal cellular targets, as the mannose metabolism, that can be further explored for the development of novel antifungals.},
doi = {10.1016/j.csbj.2021.09.007},
journal = {Computational and Structural Biotechnology Journal},
number = ,
volume = 19,
place = {United States},
year = {Mon Sep 27 00:00:00 EDT 2021},
month = {Mon Sep 27 00:00:00 EDT 2021}
}
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