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Systematic phenotyping of a large-scale Candida glabrata deletion collection reveals novel antifungal tolerance genes
- Source :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2014, 10 (6), pp.e1004211. ⟨10.1371/journal.ppat.1004211⟩, PLoS Pathogens, 2014, 10 (6), pp.e1004211. ⟨10.1371/journal.ppat.1004211⟩, Plos Pathogens 6 (10), . (2014), PLoS Pathogens, Vol 10, Iss 6, p e1004211 (2014)
- Publication Year :
- 2014
-
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.<br />Author Summary Clinical infections by the yeast-like pathogen Candida glabrata have been ever-increasing over the past years. Importantly, C. glabrata is one of the most prevalent causes of drug-refractory fungal infections in humans. We have generated a novel large-scale collection encompassing 619 bar-coded C. glabrata mutants, each lacking a single gene. Extensive profiling of phenotypes reveals a number of novel genes implicated in tolerance to antifungal drugs that interfere with proper cell wall function, as well as genes affecting fitness of C. glabrata both during normal growth and under environmental stress. This fungal deletion collection will be a valuable resource for the community to study mechanisms of virulence and antifungal drug tolerance in C. glabrata, which is particularly relevant in view of the increasing prevalence of infections caused by this important human fungal pathogen.
- Subjects :
- Azoles
Antifungal Agents
Antifungal drug
Candida glabrata
Biochemistry
biofilm
Echinocandins
Gene Knockout Techniques
chemistry.chemical_compound
MESH: Lipopeptides
Caspofungin
Cell Wall
MESH: Azoles
saccharomyces cerevisiae
délétion
Biology (General)
Candida albicans
MESH: Candida glabrata
[SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
MESH: Gene Knockout Techniques
0303 health sciences
Fungal protein
MESH: Microbial Sensitivity Tests
biology
Candidiasis
Fungal genetics
MESH: Candidiasis
phénotype
Phenotype
Medical Microbiology
antifongique
MESH: Fungal Proteins
paroi cellulaire
Functional genomics
Research Article
medicine.drug
Echinocandin
QH301-705.5
Immunology
Microbial Sensitivity Tests
MESH: Biofilms
MESH: Phenotype
Microbiology
MESH: Drug Resistance, Fungal
Fungal Proteins
Lipopeptides
pathogène fongique
03 medical and health sciences
MESH: Cell Wall
Drug Resistance, Fungal
Osmotic Pressure
Virology
MESH: Gene Library
Genetics
medicine
azole
Microbial Pathogens
Molecular Biology
Gene Library
030304 developmental biology
030306 microbiology
MESH: Echinocandins
Biology and Life Sciences
RC581-607
MESH: Osmotic Pressure
biology.organism_classification
bacterial infections and mycoses
MESH: Antifungal Agents
[SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
chemistry
MESH: Gene Deletion
Biofilms
Parasitology
Immunologic diseases. Allergy
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 15537366 and 15537374
- Database :
- OpenAIRE
- Journal :
- PLoS Pathogens, PLoS Pathogens, Public Library of Science, 2014, 10 (6), pp.e1004211. ⟨10.1371/journal.ppat.1004211⟩, PLoS Pathogens, 2014, 10 (6), pp.e1004211. ⟨10.1371/journal.ppat.1004211⟩, Plos Pathogens 6 (10), . (2014), PLoS Pathogens, Vol 10, Iss 6, p e1004211 (2014)
- Accession number :
- edsair.doi.dedup.....2a3ccb01dc6fe4ec38b19860eda57ecc