Systematic Phenotyping of a Large-Scale Candida glabrata Deletion Collection Reveals Novel Antifungal Tolerance Genes
Figure 4
Classification of C. glabrata chemogenetic profiles.
(A) Overlap between the chemical-genetic profile of CF (38 genes), CR (12 genes) and CW (6 genes). 28 genes (labeled in bold letters) were novel CF tolerance genes, since they have not been previously associated with echinocandin hypersensitivity in S. cerevisiae or C. albicans. (B) Overlap between the chemical-genetic profile of CF, azoles and AmB. 61 genes displayed an increased sensitivity to CF (38 genes plus 10 genes with weak sensitivity), azoles (14 genes; fluconazole and voriconazole) and AmB (13 genes). The mutant strain collection was screened in a 96 well microplate format using an endpoint assay and medium was supplemented with 5 µg/ml fluconazole, 100 ng/ml voriconazole and 1,5 µg/ml AmB. The OD600 was determined after 24 and 48 hours of incubation at 30°C. Grey-colored genes only display a weak sensitivity phenotype or were excluded from further analysis due to strong variations in the screening. Nodes represent compounds or genes and edges indicate chemical-genetic interactions. Gene nodes are color-coded according to GO annotation. Venn diagrams summarize distribution of genes affecting resistance to one of the three compounds.