Functional analysis of the Candida albicans kinome reveals Hrr25 as a regulator of antifungal susceptibility
Yunjin Lee, Sean D. Liston, Dongyeob Lee, Nicole Robbins, Leah E. Cowen
Abstract
kinome to identify genes for which loss-of-function confers hypersensitivity to the two most widely deployed antifungals, echinocandins and azoles. Through this analysis, we found a role for the casein kinase 1 (CK1) homologue Hrr25 in regulating tolerance to both antifungals as well as target-mediated echinocandin resistance. Follow-up investigations established that Hrr25 regulates these responses through its interaction with the SBF transcription factor. Thus, we provide insights into the circuitry governing cellular responses to antifungals and implicate Hrr25 as a key mediator of drug resistance.
Topics & Concepts
KinomeCandida albicansEchinocandinsEchinocandinCaspofunginAnidulafunginBiologyDrug resistanceAntifungal drugKinaseMediatorCasein kinase 1DrugMicafunginComputational biologyMicrobiologyAntifungalPharmacologyProtein kinase AAmphotericin BGeneticsCell biologyFluconazoleAntifungal resistance and susceptibilityFungal Infections and StudiesPlant-Microbe Interactions and Immunity