Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.tcsw.2021.100057
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dc.titleInactivating the mannose-ethanolamine phosphotransferase Gpi7 confers caspofungin resistance in the human fungal pathogen Candida albicans
dc.contributor.authorZeng, Guisheng
dc.contributor.authorXu, Xiaoli
dc.contributor.authorGao, Jiaxin
dc.contributor.authorDa Silva Dantas, Alessandra
dc.contributor.authorGow, Neil A.R.
dc.contributor.authorWang, Yue
dc.date.accessioned2022-10-13T01:06:42Z
dc.date.available2022-10-13T01:06:42Z
dc.date.issued2021-12-01
dc.identifier.citationZeng, 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. https://doi.org/10.1016/j.tcsw.2021.100057
dc.identifier.issn2468-2330
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/232725
dc.description.abstractUnderstanding 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)
dc.publisherElsevier B.V.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScopus OA2021
dc.subjectAntifungal resistance
dc.subjectCaspofungin
dc.subjectCell wall
dc.subjectChitin synthesis
dc.subjectFungal pathogens
dc.typeArticle
dc.contributor.departmentINSTITUTE OF MOLECULAR & CELL BIOLOGY
dc.description.doi10.1016/j.tcsw.2021.100057
dc.description.sourcetitleThe Cell Surface
dc.description.volume7
dc.description.page100057
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