一个祖先的真菌菌因子促进了感染的传播
Joseph W Saelens1, Mollie I Sweeney1, Gopinath Viswanathan1
1Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Cell
|November 10, 2022
概括
一种特定的 Mycobacterium tuberculosis (Mtb) 菌株具有祖先的 EsxM 蛋白质变体,通过增强巨细胞的移动性和颗粒瘤的退出,导致扩散和骨疾病的增加. 这表明EsxM调节了Mtb的传播.
科学领域:
- 微生物学
- 传染性疾病
- 病原体的演变
背景情况:
- 结核菌 (Mtb) 通常导致肺部疾病,但可以扩散到其他器官.
- 肺外MTB病,尤其是骨病,不太常见,但可能发生.
- Mtb传播潜力的遗传基础尚未得到充分理解.
研究的目的:
- 研究MTB爆发背后的分子机制,
- 确定影响传播和疾病表现的Mtb菌株的遗传因素.
- 了解第七类分泌因子EsxM在Mtb病变中的作用.
主要方法:
- 在疫情爆发后对Mtb菌株进行基因组分析.
- 在体外研究巨细胞行为 (移动性,退出,行为动力学).
- 使用斑马鱼模型进行骨病的体内研究.
主要成果:
- 这种爆发菌株含有祖先的全长EsxM变种,与现代菌株的截断版本不同.
- 祖先的EsxM增强了巨细胞的运动性,促进了巨细胞从颗粒瘤中脱离,并改变了巨细胞的活性.
- 在减弱的Mtb菌株中复制祖先的EsxM增加了巨细胞的运动性.
- 在斑马鱼模型中,全长的EsxM促进了骨病.
- 在主要的Mtb谱系中存在EsxM的衍生无意义变异,这表明它在限制传播方面的作用.
结论:
- 祖先的全长EsxM变种有助于Mtb的肺外传播和骨.
- EsxM对巨细胞行为的调节是Mtb传播的关键机制.
- 一个截断的EsxM的演变可能代表着一种控制现代血统中Mtb传播的机制.
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