Transcriptional and translational landscape of Candida auris in response to caspofungin

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.

doi:10.1016/j.csbj.2021.09.007

Title: Transcriptional and translational landscape of Candida auris in response to caspofungin

Journal Article · 26 September 2021 · Computational and Structural Biotechnology Journal

DOI: https://doi.org/10.1016/j.csbj.2021.09.007 · OSTI ID:1837548

^[1]; Amatuzzi, Rafaela F. ^[2]; Munhoz da Rocha, Isadora F. ^[2];

^[2];

^[3]; Vieira, Alexandre Z. ^[3]; Trentin, Gabriel ^[4];

^[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)

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.

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Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE; CNPq; National Institutes of Health (NIH); Fiocruz

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1837548

Report Number(s):: PNNL-SA--167223

Journal Information:: Computational and Structural Biotechnology Journal, Journal Name: Computational and Structural Biotechnology Journal Vol. 19; ISSN 2001-0370

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: English

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