TY - JOUR
T1 - Transcriptional and translational landscape of Candida auris in response to caspofungin
AU - Zamith-Miranda, Daniel
AU - Amatuzzi, Rafaela F.
AU - Munhoz da Rocha, Isadora F.
AU - Martins, Sharon T.
AU - Lucena, Aline C.R.
AU - Vieira, Alexandre Z.
AU - Trentin, Gabriel
AU - Almeida, Fausto
AU - Rodrigues, Marcio L.
AU - Nakayasu, Ernesto S.
AU - Nosanchuk, Joshua D.
AU - Alves, Lysangela R.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - 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 24 h 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.
AB - 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 24 h 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.
KW - Candida auris
KW - Drug resistance
KW - Proteomics
KW - Stress response
KW - Transcriptomics
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U2 - 10.1016/j.csbj.2021.09.007
DO - 10.1016/j.csbj.2021.09.007
M3 - Article
AN - SCOPUS:85115889445
SN - 2001-0370
VL - 19
SP - 5264
EP - 5277
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -