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Expanded role of the Cu-sensing transcription factor Mac1p in Candida albicans.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-08-18 , DOI: 10.1111/mmi.14591
Edward M Culbertson 1 , Vincent M Bruno 2 , Brendan P Cormack 3 , Valeria C Culotta 1
Affiliation  

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.

中文翻译:

Cu 感应转录因子 Mac1p 在白色念珠菌中的扩展作用。

作为先天免疫反应的一部分,宿主阻止入侵病原体的铜等金属微量营养素,微生物通过金属饥饿应激反应做出反应。对于机会性真菌病原体白色念珠菌,Cu 感应转录因子 Mac1p 通过控制 Cu 输入来控制细胞对 Cu 饥饿的反应。Mac1p 还通过抑制含铜超氧化物歧化酶 ( SOD1 ) 和诱导含锰SOD3作为非铜替代品来控制活性氧 (ROS) 稳态。我们在这里表明白色念珠菌Mac1p 对于播散性念珠菌病小鼠模型的毒力至关重要,而且 Mac1p 的细胞功能超出了 Cu 摄取和 ROS 稳态。具体来说,mac1Δ/Δ突变体在线粒体呼吸和铁积累方面存在严重缺陷,这两个过程都依赖于铜。令人惊讶的是,这些缺陷不仅仅是铜吸收受损的产物;而mac1Δ/Δ突变体在铜分配中出现缺陷。sod1∆/∆突变大大改善了mac1∆/∆突变体的呼吸缺陷,证明了SOD1的作用Mac1p 抑制呼吸作用。Mac1p 下调主要的铜消耗者 SOD1 以腾出铜进行呼吸,这对于这种真菌病原体的毒力至关重要。讨论了对其他病原真菌中这种铜稳态控制的影响。
更新日期:2020-08-18
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