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Title: Inactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen Candida albicans
Authors: Zeng, Guisheng
Xu, Xiaoli
Gao, Jiaxin
Da Silva Dantas, Alessandra
Gow, Neil A.R.
Wang, Yue 
Keywords: Antifungal resistance
Cell wall
Chitin synthesis
Fungal pathogens
Issue Date: 1-Dec-2021
Publisher: Elsevier B.V.
Citation: Zeng, Guisheng, Xu, Xiaoli, Gao, Jiaxin, Da Silva Dantas, Alessandra, Gow, Neil A.R., Wang, Yue (2021-12-01). Inactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen Candida albicans. The Cell Surface 7 : 100057. ScholarBank@NUS Repository.
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Understanding the molecular mechanisms governing antifungal resistance is crucial for identifying new cellular targets for developing new antifungal therapeutics. In this study, we performed a transposon-mediated genome-wide genetic screen in haploid Candida albicans to identify mutants resistant to caspofungin, the first member of the echinocandin class of antifungal drugs. A mutant exhibiting the highest resistance possessed a transposon insertion that inactivates GPI7, a gene encoding the mannose-ethanolamine phosphotransferase. Deleting GPI7 in diploid C. albicans caused similar caspofungin resistance. gpi7?/? cells showed significantly elevated cell wall chitin content and enhanced phosphorylation of Mkc1, a core component of the PKC-MAPK cell-wall integrity pathway. Deleting MKC1 suppressed the chitin elevation and caspofungin resistance of gpi7?/? cells, but overexpressing the dominant inactive form of RHO1, an upstream activator of PKC-MAPK signaling, did not. Transcriptome analysis uncovered 406 differentially expressed genes in gpi7?/? cells, many related to cell wall construction. Our results suggest that GPI7 deletion impairs cell wall integrity, which triggers the cell-wall salvage mechanism via the PKC-MAPK pathway independently of Rho1, resulting in the compensatory chitin synthesis to confer caspofungin resistance. © 2021 The Author(s)
Source Title: The Cell Surface
ISSN: 2468-2330
DOI: 10.1016/j.tcsw.2021.100057
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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