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Expanded role of the Cu‐sensing transcription factor Mac1p in Candida albicans
Author(s) -
Culbertson Edward M.,
Bruno Vincent M.,
Cormack Brendan P.,
Culotta Valeria C.
Publication year - 2020
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.14591
Subject(s) - candida albicans , biology , microbiology and biotechnology , virulence , mutant , superoxide dismutase , transcription factor , reactive oxygen species , homeostasis , corpus albicans , psychological repression , pathogen , oxidative stress , biochemistry , gene , gene expression
As part of the innate immune response, the host withholds metal micronutrients such as Cu from invading pathogens, and microbes respond through metal starvation stress responses. With the opportunistic fungal pathogen Candida albicans , the Cu‐sensing transcription factor Mac1p governs the cellular response to Cu starvation by controlling Cu import. Mac1p additionally controls reactive oxygen species (ROS) homeostasis by repressing a Cu‐containing superoxide dismutase ( SOD1 ) and inducing Mn‐containing SOD3 as a non‐Cu alternative. We show here that C. albicans Mac1p is essential for virulence in a mouse model for disseminated candidiasis and that the cellular functions of Mac1p extend beyond Cu uptake and ROS homeostasis. Specifically, mac1∆/∆ mutants are profoundly deficient in mitochondrial respiration and Fe accumulation, both Cu‐dependent processes. Surprisingly, these deficiencies are not simply the product of impaired Cu uptake; rather mac1∆/∆ mutants appear defective in Cu allocation. The respiratory defect of mac1∆/∆ mutants was greatly improved by a sod1∆/∆ mutation, demonstrating a role for SOD1 repression by Mac1p in preserving respiration. Mac1p downregulates the major Cu consumer SOD1 to spare Cu for respiration that is essential for virulence of this fungal pathogen. The implications for such Cu homeostasis control in other pathogenic fungi are discussed.