在Mycobacterium tuberculosis中PE/PPE基因的持续演变与耐药性和宿主免疫反应相关
Mingyu Gan1,2, Dan Wang3, Suqing Li3
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
在Mycobacterium tuberculosis中,proline-glutamate/proline-proline-glutamate (PE/PPE) 基因家族显示了放松的净化选择和适应抗生素耐药性和宿主免疫力. 像PPE51这样的特定基因可能对多药耐药菌株的生存至关重要.
科学领域:
- 基因组学就是基因组学.
- 进化生物学 进化生物学
- 微生物学 微生物学
背景情况:
- 氨酸酸盐/氨酸酸酸盐 (PE/PPE) 基因家族构成Mycobacterium tuberculosis (Mtb) 基因组的10%左右.
- PE/PPE基因中的重复序列和高GC含量阻碍了通过短读序列测序进行分析,限制了对它们的多样性和演变的理解.
- 基因组掩盖的近期进展使PE/PPE序列从短读数据中恢复成为可能,从而促进了人口层面的进化研究.
研究的目的:
- 在MtbPE/PPE基因家族内描述序列多样性和选择压力.
- 为了确定PE/PPE基因在积极选择下或与抗生素耐药性相关.
- 探索PE/PPE基因在适应宿主免疫和药物压力的潜在作用.
主要方法:
- 使用基因组掩盖方法分析了51,229万亿的基因组.
- 对序列多样性和选择压力的评估 (例如,pNpS比率,突变负担).
- 在积极选择下识别基因,抗生素耐药性压力和多样化选择.
主要成果:
- 与其他基因类别相比,PE/PPE基因表现出放松的净化选择,具有更高的突变负担.
- 十二个PE/PPE基因显示积极选择的特征,七个与抗生素耐药性有关.
- 在多药耐药菌株中观察到PPE51功能丧失突变,这表明了适应性;六个PE/PPE基因在多样化选择下具有T细胞表位.
结论:
- PE/PPE基因在Mtb适应抗生素压力和宿主免疫力方面发挥着重要作用.
- 特定的PE/PPE基因,包括PPE51,是理解和打击耐药性的潜在目标.
- 在PE/PPE基因中发现免疫驱动的适应性为新型疫苗开发策略提供了途径.
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