文章基本信息

标题：Functional analysis of the Candida albicans kinome reveals Hrr25 as a regulator of antifungal susceptibility
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作者：Yunjin Lee ; Sean D. Liston ; Dongyeob Lee 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：6
页码：1-18
DOI：10.1016/j.isci.2022.104432
语种：English
出版社：Elsevier
摘要：SummaryCandida albicansis a leading cause of death due to systemic fungal infections. Poor patient outcomes are attributable to the limited number of antifungal classes and the increasing prevalence of drug resistance. Protein kinases have emerged as rewarding targets in the development of drugs for diverse diseases, yet kinases remain untapped in the quest for new antifungals. Here, we performed a comprehensive analysis of theC. albicanskinome 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.Graphical abstractDisplay OmittedHighlights•ScreeningCandida albicanskinase mutants reveals 47 regulators of antifungal tolerance•Hrr25 is important for growth and cell wall/membrane stress tolerance•Hrr25 enables target-mediated echinocandin resistance•Hrr25 interacts with the SBF transcription factor complexBiological sciences; Molecular biology; Microbiology