Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes.
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 imp...
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2014
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oai:doaj.org-article:986a5b5ef3804428b35fc96b095e2b8a2021-11-11T06:06:08ZSystematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes.1553-73661553-737410.1371/journal.ppat.1004211https://doaj.org/article/986a5b5ef3804428b35fc96b095e2b8a2014-06-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24945925/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374The 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.Tobias SchwarzmüllerBiao MaEkkehard HillerFabian IstelMichael TschernerSascha BrunkeLauren AmesArnaud FironBrian GreenVitor CabralMarina Marcet-HoubenIlse D JacobsenJessica QuintinKatja SeiderIngrid FrohnerWalter GlaserHelmut JungwirthSophie Bachellier-BassiMurielle ChauvelUte ZeidlerDominique FerrandonToni GabaldónBernhard HubeChristophe d'EnfertSteffen RuppBrendan CormackKen HaynesKarl KuchlerPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 6, p e1004211 (2014) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Tobias Schwarzmüller Biao Ma Ekkehard Hiller Fabian Istel Michael Tscherner Sascha Brunke Lauren Ames Arnaud Firon Brian Green Vitor Cabral Marina Marcet-Houben Ilse D Jacobsen Jessica Quintin Katja Seider Ingrid Frohner Walter Glaser Helmut Jungwirth Sophie Bachellier-Bassi Murielle Chauvel Ute Zeidler Dominique Ferrandon Toni Gabaldón Bernhard Hube Christophe d'Enfert Steffen Rupp Brendan Cormack Ken Haynes Karl Kuchler Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| description |
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. |
| format |
article |
| author |
Tobias Schwarzmüller Biao Ma Ekkehard Hiller Fabian Istel Michael Tscherner Sascha Brunke Lauren Ames Arnaud Firon Brian Green Vitor Cabral Marina Marcet-Houben Ilse D Jacobsen Jessica Quintin Katja Seider Ingrid Frohner Walter Glaser Helmut Jungwirth Sophie Bachellier-Bassi Murielle Chauvel Ute Zeidler Dominique Ferrandon Toni Gabaldón Bernhard Hube Christophe d'Enfert Steffen Rupp Brendan Cormack Ken Haynes Karl Kuchler |
| author_facet |
Tobias Schwarzmüller Biao Ma Ekkehard Hiller Fabian Istel Michael Tscherner Sascha Brunke Lauren Ames Arnaud Firon Brian Green Vitor Cabral Marina Marcet-Houben Ilse D Jacobsen Jessica Quintin Katja Seider Ingrid Frohner Walter Glaser Helmut Jungwirth Sophie Bachellier-Bassi Murielle Chauvel Ute Zeidler Dominique Ferrandon Toni Gabaldón Bernhard Hube Christophe d'Enfert Steffen Rupp Brendan Cormack Ken Haynes Karl Kuchler |
| author_sort |
Tobias Schwarzmüller |
| title |
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| title_short |
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| title_full |
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| title_fullStr |
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| title_full_unstemmed |
Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| title_sort |
systematic phenotyping of a large-scale candida glabrata deletion collection reveals novel antifungal tolerance genes. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/986a5b5ef3804428b35fc96b095e2b8a |
| work_keys_str_mv |
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| _version_ |
1718439515722350592 |