Systematic phenotyping of a large-scale candida glabrata deletion collection reveals novel antifungal tolerance genes

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• dc.contributor.author Schwarzmüller, Tobias
• dc.contributor.author Gabaldón Estevan, Juan Antonio, 1973-
• dc.contributor.author Kuchler, Karl
• dc.date.accessioned 2025-01-14T08:13:12Z
• dc.date.available 2025-01-14T08:13:12Z
• dc.date.issued 2014
• dc.description.abstract The opportunistic fungal pathogen Candida glabrata is a frequent cause of candidiasis, causing infections ranging from superficial to life-threatening disseminated disease. The inherent tolerance of C. glabrata to azole drugs makes this pathogen a serious clinical threat. To identify novel genes implicated in antifungal drug tolerance, we have constructed a large-scale C. glabrata deletion library consisting of 619 unique, individually bar-coded mutant strains, each lacking one specific gene, all together representing almost 12% of the genome. Functional analysis of this library in a series of phenotypic and fitness assays identified numerous genes required for growth of C. glabrata under normal or specific stress conditions, as well as a number of novel genes involved in tolerance to clinically important antifungal drugs such as azoles and echinocandins. We identified 38 deletion strains displaying strongly increased susceptibility to caspofungin, 28 of which encoding proteins that have not previously been linked to echinocandin tolerance. Our results demonstrate the potential of the C. glabrata mutant collection as a valuable resource in functional genomics studies of this important fungal pathogen of humans, and to facilitate the identification of putative novel antifungal drug target and virulence genes.en
• dc.description.sponsorship This work was supported by the Austrian Science Foundation FWF through the ERA-Net Pathogenomics project FunPath to KK (FWF-API-0125), SR (BMBF: 0313931A), TG, CD, DF and BH, and in part by the Christian Doppler Society to KK. BC and BM were supported in part by NIH RO1AI46223. BH and SB were supported by the German Federal Ministry of Education and Research (BMBF) through FKZ: 01EO1002. TG was funded in part by grants from the Spanish ministry of science and innovation (GEN2006-27784E, BFU2009-09168). KH was funded by the BBSRC (BB/F005210/1). DF was also partly supported by CNRS and the Fondation pour la recherche Médicale (Programme Equipe FRM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
• dc.format.mimetype application/pdf
• dc.identifier.citation Schwarzmüller T, Ma B, Hiller E, Istel F, Tscherner M, Brunke S, et al. Systematic phenotyping of a large-scale candida glabrata deletion collection reveals novel antifungal tolerance genes. PLoS Pathog. 2014 Jun 19;10(6):e1004211. DOI: 10.1371/journal.ppat.1004211
• dc.identifier.doi http://dx.doi.org/10.1371/journal.ppat.1004211
• dc.identifier.issn 1553-7374
• dc.identifier.uri http://hdl.handle.net/10230/69095
• dc.language.iso eng
• dc.publisher Public Library of Science (PLoS)
• dc.relation.ispartof PLoS Pathogens. 2014 Jun 19;10(6):e1004211
• dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2009-09168
• dc.rights © 2014 Schwarzmüller et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Biofilmsca
• dc.subject.other Ecologia microbianaca
• dc.subject.other Càndidaca
• dc.title Systematic phenotyping of a large-scale candida glabrata deletion collection reveals novel antifungal tolerance genesen
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion