林代谢是促进Candida albicans病原性的一个关键因素
Fitz Gerald S Silao1, Tong Jiang2, Biborka Bereczky-Veress3
1Department of Molecular Biosciences, The Wenner-Gren Institute, Science for Life Laboratory, Stockholm University, Solna, Sweden.
PLoS pathogens
|November 2, 2023
概括
虫 Candida albicans 使用普罗林作为能量和生长的来源. 破坏proline利用基因会损害其毒性和切换形式的能力,突出显示proline代谢.
科学领域:
- 医学真菌学 医学真菌学
- 分子生物学分子生物学
- 病原体的新陈代谢
背景情况:
- 菌 (Candida albicans) 是人类真菌感染 (真菌菌) 的主要原因之一.
- 这种真菌利用普罗林作为能量,生长和形态转换 (酵母转化为形).
研究的目的:
- 为了研究在Candida albicans病毒性中proline利用 (UT) 基因的作用.
- 为了了解proline代谢缺陷对真菌病原和宿主相互作用的影响.
主要方法:
- 对林利用基因的基因操纵 (put1-/-, put2-/-).
- 对普罗林敏感性和罗林-5-碳酸盐 (P5C) 积累的评估.
- 在Drosophila和小鼠候群病模型中对毒性的评估.
- 分析人类中性粒细胞和全血中的真菌存活率.
- 脏感染的实时成像使用静脉内2光子和非线性显微镜.
主要成果:
- put1-/-和put2-/-突变体表现出对普罗林的敏感性,而put2-/-由于有毒的P5C积累抑制呼吸而过敏.
- 这些突变在昆虫和哺乳动物模型中显著减弱了毒性.
- 缺陷的普罗林利用减少了人类免疫细胞和血液中的真菌存活率.
- 在体内成像显示,在脏感染期间,put2-/-突变体的形态切换受损.
- 氨酸代谢对于包括C. auris在内的Candida物种的繁荣至关重要.
结论:
- 氨酸的利用对于Candida albicans的毒性和宿主中的适应是必不可少的.
- 普罗林代谢的缺陷,特别是P5C的积累,损害了真菌的健康和病原性.
- 准林代谢途径可能是对抗坎迪达菌感染的新策略.
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