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介体复合物在真菌发病机制和抗真菌药物反应中的作用。

The role of the Mediator complex in fungal pathogenesis and response to antifungal agents.

机构信息

Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental University Hospital, University of Dublin, Trinity College Dublin, Dublin, Ireland.

出版信息

Essays Biochem. 2023 Sep 13;67(5):843-851. doi: 10.1042/EBC20220238.

DOI:10.1042/EBC20220238
PMID:37013399
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10500203/
Abstract

Mediator is a complex of polypeptides that plays a central role in the recruitment of RNA polymerase II to promoters and subsequent transcriptional activation in eukaryotic organisms. Studies have now shown that Mediator has a role in regulating expression of genes implicated in virulence and antifungal drug resistance in pathogenic fungi. The roles of specific Mediator subunits have been investigated in several species of pathogenic fungi, particularly in the most pathogenic yeast Candida albicans. Uniquely, pathogenic yeast also present several interesting examples of divergence in Mediator structure and function, most notably in C. glabrata, which possesses two orthologues of Med15, and in C. albicans, which has a massively expanded family of Med2 orthologues known as the TLO gene family. This review highlights specific examples of recent progress in characterizing the role of Mediator in pathogenic fungi.

摘要

中介体是一种多肽复合物,在真核生物中,它在 RNA 聚合酶 II 招募到启动子并随后进行转录激活中起着核心作用。研究表明,中介体在调节与致病性真菌毒力和抗真菌药物耐药性相关的基因表达方面发挥作用。在几种致病性真菌中,特别是在最具致病性的酵母白色念珠菌中,已经研究了特定中介体亚基的作用。独特的是,致病性酵母在中介体结构和功能上也存在一些有趣的分化例子,最值得注意的是在光滑念珠菌中,它拥有两个 Med15 的同源物,而在白色念珠菌中,它拥有一个大量扩展的 Med2 同源物家族,称为 TLO 基因家族。这篇综述强调了最近在表征中介体在致病性真菌中的作用方面取得的具体进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/10500203/a0a499eb4ce0/ebc-67-ebc20220238-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/10500203/00c2712bd7f9/ebc-67-ebc20220238-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/10500203/a0a499eb4ce0/ebc-67-ebc20220238-g2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/10500203/00c2712bd7f9/ebc-67-ebc20220238-g1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/212a/10500203/a0a499eb4ce0/ebc-67-ebc20220238-g2.jpg

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The role of the Mediator complex in fungal pathogenesis and response to antifungal agents.介体复合物在真菌发病机制和抗真菌药物反应中的作用。
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引用本文的文献

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Deletion of the Candida albicans TLO gene family results in alterations in membrane sterol composition and fluconazole tolerance.敲除白念珠菌 TLO 基因家族导致膜甾醇组成和氟康唑耐受性改变。
PLoS One. 2024 Aug 9;19(8):e0308665. doi: 10.1371/journal.pone.0308665. eCollection 2024.
2
Use of a SC5314 PacBio HiFi reads dataset to close gaps in the reference genome assembly, reveal a subtelomeric gene family, and produce accurate phased allelic sequences.利用 SC5314PacBio HiFi 读取数据集来弥合参考基因组组装中的缺口,揭示端粒外基因家族,并生成准确的相定等位基因序列。
Front Cell Infect Microbiol. 2024 Feb 1;14:1329438. doi: 10.3389/fcimb.2024.1329438. eCollection 2024.
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本文引用的文献

1
Mediator Subunit Med15 Regulates Cell Morphology and Mating in .中介亚基Med15调节……中的细胞形态和交配
J Fungi (Basel). 2023 Mar 8;9(3):333. doi: 10.3390/jof9030333.
2
A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols.一种小分子 Erg251 抑制剂通过抑制 14α-甲基固醇的合成使氟康唑具有杀真菌作用。
mBio. 2023 Feb 28;14(1):e0263922. doi: 10.1128/mbio.02639-22. Epub 2022 Dec 8.
3
Architectural groups of a subtelomeric gene family evolve along distinct paths in Candida albicans.
Deletion of the Candida albicans TLO gene family using CRISPR-Cas9 mutagenesis allows characterisation of functional differences in α-, β- and γ- TLO gene function.
利用 CRISPR-Cas9 诱变技术删除白念珠菌 TLO 基因家族,可用于研究 α-、β-和 γ-TLO 基因功能的功能差异。
PLoS Genet. 2023 Dec 4;19(12):e1011082. doi: 10.1371/journal.pgen.1011082. eCollection 2023 Dec.
着丝粒基因家族的结构群在白念珠菌中沿着不同的路径进化。
G3 (Bethesda). 2022 Dec 1;12(12). doi: 10.1093/g3journal/jkac283.
4
Erg6p is essential for antifungal drug resistance, plasma membrane properties and cell wall integrity in Candida glabrata.在光滑念珠菌中,Erg6p 对于抗真菌药物耐药性、质膜特性和细胞壁完整性是必需的。
FEMS Yeast Res. 2022 Sep 24;21(1). doi: 10.1093/femsyr/foac045.
5
The Mediator complex as a master regulator of transcription by RNA polymerase II.中介体复合物作为 RNA 聚合酶 II 转录的主调控因子。
Nat Rev Mol Cell Biol. 2022 Nov;23(11):732-749. doi: 10.1038/s41580-022-00498-3. Epub 2022 Jun 20.
6
Prevalence and Healthcare Burden of Fungal Infections in the United States, 2018.2018年美国真菌感染的患病率及医疗负担
Open Forum Infect Dis. 2022 Jan 10;9(1):ofab593. doi: 10.1093/ofid/ofab593. eCollection 2022 Jan.
7
AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models.AlphaFold 蛋白质结构数据库:用高精度模型极大地扩展蛋白质序列空间的结构覆盖范围。
Nucleic Acids Res. 2022 Jan 7;50(D1):D439-D444. doi: 10.1093/nar/gkab1061.
8
Highly accurate protein structure prediction with AlphaFold.利用 AlphaFold 进行高精度蛋白质结构预测。
Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2. Epub 2021 Jul 15.
9
Precise Expression of Is Crucial for Asexual Development, Virulence, and Survival of Aspergillus fumigatus.精准表达 对于烟曲霉的无性发育、毒力和生存至关重要。
mSphere. 2020 Oct 7;5(5):e00771-20. doi: 10.1128/mSphere.00771-20.
10
Functional information from clinically-derived drug resistant forms of the Candida glabrata Pdr1 transcription factor.从临床获得的 Candida glabrata Pdr1 转录因子耐药形式中获取功能信息。
PLoS Genet. 2020 Aug 25;16(8):e1009005. doi: 10.1371/journal.pgen.1009005. eCollection 2020 Aug.