Functional portrait of the Candidozyma auris kinome
Candidozyma auris is an emerging pathogenic yeast of global health concern. We constructed two independent signature-tagged mutant libraries covering 96.4% of the predicted C. auris kinome, using a dual genetic perturbation tool allowing kinase gene overexpression and repression through a tetracycline derivative-regulatable promoter system. Phenotypic and competitive fitness profiling identified 10 fitness-defect kinases and uncovered additional ones linked to cellular morphogenesis. Stress-response profiling mapped kinase requirements onto two conserved MAPK cascades governing cell-wall integrity and onto distinct modules controlling the mitotic checkpoint and DNA-damage response. Nutrient-based profiling serendipitously revealed that C. auris undergoes filamentous and invasive growth in the presence of oleic acid-containing carbon sources. Library screening identified positive (Cek1, Swe1, Mps1) and negative (Cdc5) regulators of both processes, and others with opposing functions (Hsl1, Cbk1, Yck2), highlighting the complexity of C. auris morphogenetic kinase circuitry. Our library constitutes a versatile resource for dissecting C. auris pathobiology and for kinase-directed antifungal discovery.