Expanded role of the Cu-sensing transcription factor Mac1p in Candida albicans.
Expanded role of the Cu-sensing transcription factor Mac1p in Candida albicans.
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Cu传感转录因子MAC1P在白色念珠菌中的作用扩大。
DOI：
10.1111/mmi.14591
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发表时间：
2020-12
影响因子：
3.6
通讯作者：
Culotta VC
中科院分区：
文献类型：
--
作者：
Culbertson EM;Bruno VM;Cormack BP;Culotta VC
作为先天免疫反应的一部分，宿主抑制金属微量营养素如Cu免受入侵病原体的侵害，微生物通过金属饥饿应激反应作出反应。在条件致病真菌白色念珠菌中，Cu敏感转录因子Mac 1 p通过控制Cu输入来控制细胞对Cu饥饿的反应。Mac 1 p还通过抑制含Cu的超氧化物歧化酶（SOD 1）和诱导含Mn的SOD 3作为非Cu替代物来控制活性氧（ROS）体内平衡。我们在这里表明，C。白色念珠菌Mac 1 p在播散性念珠菌病小鼠模型中的毒力是必不可少的，Mac 1 p的细胞功能超出了Cu摄取和ROS稳态。具体而言，mac 1 Δ/Δ突变体在线粒体呼吸和Fe积累方面存在严重缺陷，这两个过程都依赖于Cu。令人惊讶的是，这些缺陷不仅仅是铜吸收受损的产物，而是mac 1 Δ/Δ突变体在铜分配方面出现缺陷。mac 1 Δ/Δ突变体的呼吸缺陷通过sod 1 Δ/Δ突变得到了极大的改善，证明了Mac 1 p对SOD 1的抑制在保护呼吸中的作用。Mac 1 p下调主要铜消费者SOD 1，以节省铜呼吸，这是必不可少的这种真菌病原体的毒力。在其他病原真菌等铜稳态控制的影响进行了讨论。在许多真菌中，铜敏感转录因子Mac 1 p诱导铜进口机制在铜限制的转录。在机会致病真菌白色念珠菌中，Mac 1 p具有额外的调节活性氧稳态的功能，涉及下调主要铜消费者Sod 1 p。Sod 1 p的这种调节具有额外的目的，即在播散性念珠菌病的小鼠模型中，为线粒体呼吸和毒力所必需的细胞色素C氧化酶保留Cu。
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, mac1Δ/Δ 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 mac1Δ/Δ mutants appear defective in Cu allocation. The respiratory defect of mac1Δ/Δ mutants was greatly improved by a sod1Δ/Δ mutation, demonstrating a role for SOD1 repression by Mac1p in preserving respiration. Mac1p down-regulates 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. Across numerous fungi, the Cu-sensing transcription factor Mac1p induces transcription of the Cu import machinery during Cu limitation. In the opportunistic fungal pathogen Candida albicans, Mac1p has the added function of regulating homeostasis of reactive oxygen species involving down-regulation of the major Cu consumer Sod1p. This regulation of Sod1p has the added purpose of sparing Cu for cytochrome C oxidase essential for mitochondrial respiration and for virulence in a murine model of disseminated candidiasis.
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影响因子：
30.3
作者：
Chen C;Pande K;French SD;Tuch BB;Noble SM
通讯作者：
Noble SM
影响因子：
3
作者：
Gleason, Julie E.;Li, Cissy X.;Odeh, Hana M.;Culotta, Valeria C.
通讯作者：
Culotta, Valeria C.
影响因子：
3.6
作者：
Ding C;Yin J;Tovar EM;Fitzpatrick DA;Higgins DG;Thiele DJ
通讯作者：
Thiele DJ
铜限制对开放海洋硅藻塔拉西奥拉海洋两种菌株光合作用的对比影响。
影响因子：
3.7
作者：
Hippmann AA;Schuback N;Moon KM;McCrow JP;Allen AE;Foster LJ;Green BR;Maldonado MT
通讯作者：
Maldonado MT
影响因子：
--
作者：
Conti, Heather R;Huppler, Anna R;Whibley, Natasha;Gaffen, Sarah L
通讯作者：
Gaffen, Sarah L