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在一个机会主义的人类肺病原体中,de novo突变调解了表型转换
Alexandra J Poret1,2,3, Matthew Schaefers4,5, Christina Merakou4,5
1Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Nature communications
|July 23, 2025
概括
囊性纤维化患者的Burkholderia dolosa通过交替O-抗原表达迅速演变. 这种细菌适应策略有助于克服感染期间的环境权衡,强调了时间采样的重要性.
科学领域:
- 微生物学 微生物学
- 进化生物学 进化生物学
- 传染性疾病 传染性疾病
背景情况:
- 在人类宿主中进化的细菌面临选择性权衡,突变在某种情况下可能是有益的,在另一个情况下可能是有害的.
- 已知与囊性纤维化相关的病原体Burkholderia dolosa能够适应人类宿主环境.
研究的目的:
- 研究Burkholderia dolosa如何通过连续的点突变克服人类的选择性权衡.
- 了解O-抗原表达在囊性纤维化感染期间细菌适应中的作用.
主要方法:
- 来自新感染和慢性感染囊性纤维化患者的931个呼吸道分离物的全基因组测序.
- 与同一爆发菌株的112个历史基因组进行比较基因组分析.
- 对O-抗原损失和恢复表型的实验性表征.
主要成果:
- 在新感染的患者中迅速出现了破坏O-抗原表达的融合突变,在3年内主导了B. dolosa社区.
- 这种快速的O-抗原损失与以前在慢性感染期间恢复O-抗原的发现形成鲜明对比.
- O-抗原损失增强了免疫细胞的吸收,但降低了小鼠肺部的竞争力.
结论:
- 通过连续突变的表型交替使Burkholderia dolosa能够在人类宿主中进行选择性权衡.
- O-抗原表达的优势取决于上下文,受组织局部化和感染持续时间的影响.
- 密集的时间采样对于检测长期感染的微生物中突变驱动的表型交替至关重要.
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