Please use this identifier to cite or link to this item:
DC FieldValue
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.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.
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.sourceScopus OA2021
dc.subjectAntifungal resistance
dc.subjectCell wall
dc.subjectChitin synthesis
dc.subjectFungal pathogens
dc.contributor.departmentINSTITUTE OF MOLECULAR & CELL BIOLOGY
dc.description.sourcetitleThe Cell Surface
Appears in Collections:Elements
Staff Publications

Show simple item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1016_j_tcsw_2021_100057.pdf5.8 MBAdobe PDF




checked on Jan 30, 2023

Page view(s)

checked on Feb 2, 2023

Google ScholarTM



This item is licensed under a Creative Commons License Creative Commons