在高CO2中Cryptococcus neoformans的微进化趋于从复发性加密球菌病患者中分离出来的突变
Benjamin J Chadwick1, Laura C Ristow2, Emma E Blackburn3
1Department of Plant Biology, University of Georgia, Athens, GA 30602, USA.
Cell reports
|February 25, 2025
概括
新型菌通过微观进化适应宿主二氧化碳 (CO2) 水平. 在Avc1中失去功能的突变赋予了CO2耐受性,增加了真菌毒性,并解释了复发性感染.
科学领域:
- 医学真菌学 医学真菌学
- 微生物病原体的产生
- 进化生物学 进化生物学
背景情况:
- 新型菌 (Cryptococcus neoformans) 导致严重的感染,每年有18万例死亡.
- 的毒性与适应宿主特定环境有关,例如高二氧化碳水平.
- 环境菌株对哺乳动物组织中发现的5%的二氧化碳有不同的耐受性.
研究的目的:
- 研究微观进化的作用在Cryptococcus neoformans适应宿主CO2的过程中.
- 确定赋予二氧化碳耐受性和增加毒性的遗传机制.
- 确定二氧化碳适应在加密球菌病原体中的重要性.
主要方法:
- 环境和宿主适应的C. neoformans菌株的比较基因组学.
- 在高二氧化碳条件下分析微观进化变化.
- 功能性研究涉及基因删除 (AVC1) 和真菌适应性 in vitro 和 in vivo 的评估.
主要成果:
- 在高CO2的微进化导致核酸结合蛋白Avc1.1的功能丧失突变.
- Avc1突变赋予以前不耐受菌株的二氧化碳耐受性.
- 删除AVC1增强宿主CO2条件和小鼠模型中的真菌适应性,在复发患者隔离物中发现了类似突变.
结论:
- 对宿主CO2的适应是C. neoformans在感染期间适应性的关键驱动因素.
- 在AVC1突变上的微进化趋同解释了病毒性增加和复发性加密球菌病.
- 针对二氧化碳适应途径可能提供新的治疗策略.
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