核心组织蛋白控制着Candida glabrata中的 Echinocandin 敏感性
Aditi Pareek1,2, Rupinder Kaur1
1Laboratory of Fungal Pathogenesis, Centre for DNA Fingerprinting and Diagnostics, Hyderabad, India.
Microbiology spectrum
|April 30, 2025
概括
在Candida glabrata中减少的核心素水平增加了对类抗真菌药物的敏感性,影响了药物耐药性. 希斯H3乙化是卡斯波金反应的关键,提供了潜在的治疗点.
科学领域:
- 菌类学 菌类学是指菌类学.
- 分子生物学分子生物学
- 抗微生物耐药性 抗微生物耐药性
背景情况:
- 染色素结构对于真菌生物过程至关重要.
- 组织蛋白在抗真菌药物敏感性中的作用在很大程度上是未知的.
- 虫 (Candida glabrata) 呈现出越来越多的抗 Echinocandin 抗真菌剂的耐药性.
研究的目的:
- 为了研究基因组基因剂量的作用在Candida glabrata中的 echinocandin 敏感性.
- 为了阐明核心组织蛋白水平对真菌耐药性的影响.
- 探索素H3乙化对卡斯波金反应的参与.
主要方法:
- 在Candida glabrata中生成和表征单基因组和双基因组突变.
- 评估药物对类类抗真菌药物的敏感性.
- 分析反应性氧物种的产生,生物膜的形成和DNA损伤.
- 在lysine-56及其相关酶中对基因素H3乙化进行研究.
主要成果:
- 减少基因对核心基因素 (H2A,H2B,H3,H4) 的剂量增加了 echinocandin 的敏感性.
- 链接组合素H1的损失没有影响药物敏感性.
- 核心组织素突变体显示ROS产量下降,生物膜变化和DNA损伤增加.
- 在 lysine-56 (H3K56Ac) 处的 histone H3 乙化对于 caspofungin 的反应至关重要.
结论:
- 歇斯剂量是Candida glabrata中 echinocandin 敏感性的关键调节者.
- 向组素蛋白可能提供一种克服 echinocandin 耐药性的策略.
- 基斯修饰,特别是H3K56Ac,在抗真菌药物反应中起着重要作用.
相关概念视频
Histone Modification
12.8K
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
12.8K
Histone Variants at the Centromere
4.3K
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
4.3K
Spreading of Chromatin Modifications
8.1K
The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
Writers
The writer...
8.1K
The Nucleosome Core Particle
799
Nucleosomes are the DNA-histone complex, where the DNA strand is wound around the histone core. The histone core is an octamer containing two copies of H2A, H2B, H3, and H4 histone proteins.
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
Nucleosomes, paradoxically, perform two opposite functions simultaneously. On the one hand, their primary aim is to protect the delicate DNA strands from physical damage and help achieve a higher compaction ratio. On the other hand, they must allow polymerase enzymes to access histone-bound DNA during...
799
Euchromatin
6.7K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
6.7K
Heterochromatin
9.0K
The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
9.0K


