与膜相关的J-域蛋白,Caj1的特异性,在发芽酵母中的安福特里辛B耐受性中
Preeti Sagarika1, Neha Dobriyal2, Pakirisamy Deepsika1
1Department of Biological Sciences, IISER, Bhopal, India.
Molecular microbiology
|September 18, 2024
概括
J-域蛋白Caj1通过保持血膜完整性来保护酵母免受抗真菌药物安福特里辛B的影响. 删除Caj1增加了对这种药物的敏感性,突出了它在真菌药物耐受性中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 菌类学 菌类学是指菌类学.
- 生物化学 生物化学
背景情况:
- Hsp70:J-域蛋白 (JDP) 机械对于细胞蛋白质稳定和真菌生理学至关重要.
- Hsp70有助于抗真菌药物耐受性,但JDP的作用不太清楚.
- 氨酸B (AmB) 是一种广泛使用的抗真菌药物,向真菌的血膜.
研究的目的:
- 调查细胞质JDPs在芽酵母对AMB的敏感性中的作用.
- 确定JDP Caj1对AmB耐受性的具体贡献.
主要方法:
- 在芽酵母中对细胞质JDP进行删除菌株分析.
- 在酵母菌株中对AmB敏感性的评估.
- 对血完整性标记物的分析 (例如,酸盐流出).
- 调查Caj1域和调控因素,如植物素 (PHS) 和PMP3.3的作用.
主要成果:
- 删除Caj1,一个与血相关的JDP,显著增加了AMB敏感性.
- Caj1对AmB的保护作用需要其J域和脂质结合域.
- Caj1 缺乏导致了血膜完整性的损害和酸盐流量增加.
- 升高的温度加剧了caj1Δ细胞中的AmB敏感性.
- 添加光素 (PHS) 和PMP3过度表达挽救了caj1Δ细胞中的AmB敏感性.
结论:
- Caj1与等离子体膜结合,并与Hsp70一起工作,以维持蛋白质稳定和完整性.
- 血中Caj1功能的丧失会损害蛋白质质量控制,增加对AmB的敏感性.
- 通过保持血膜完整性,Caj1是真菌耐药性的关键因素.
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