退化结核病的宿主-病原体关系与主要的瑞芬素耐药性转移突变
Nguyen Thi Le Hang1, Minako Hijikata2, Shinji Maeda3
1NCGM-BMH Medical Collaboration Center, Hanoi, Vietnam.
Frontiers in microbiology
|July 20, 2023
概括
宿主防御系统受到耐利芬素的Mycobacterium结核病突变的影响. 特定的rpoB突变,如H445Y,与主体免疫反应的改变有关,特别是干扰素通路的降低调节,这表明需要针对性结核病治疗.
科学领域:
- 结核病研究 结核病研究
- 宿主-病原体相互作用
- 基因组学和转录基因组学
背景情况:
- 结核病 (TB) 的结果受宿主防御机制和Mycobacterium tuberculosis (Mtb) 遗传突变的影响.
- 众所周知,Mtb中的利芬素 (RIF) 耐药性转移突变会影响疾病的进展.
- 在临床环境中,对具有特定突变的Mtb菌株宿主反应的全面研究是有限的.
研究的目的:
- 调查与主要rpoB突变相关的临床-流行病学因素和血液转录基因特征,使Mtb.具有RIF耐药性.
- 分析感染了携带特定rpoB突变 (H445Y和S450L) 的Mtb菌株的患者宿主免疫反应.
主要方法:
- 来自越南295名活跃肺结核患者的Mtb分离物的全基因组测序.
- 来自携带rpoB H445Y或rpoB S450L突变的Mtb感染的HIV阴性患者的全血样本的RNA测序.
- 实时RT-PCR测量特定基因的RNA表达水平.
- 逻辑和线性回归模型用于评估关联.
主要成果:
- rpoB S450L (36.8%) 和rpoB H445Y (17.2%) 是主要的RIF抗性突变.
- H445Y与北京基因型,Rv1830突变以及之前的结核病治疗发作有关.
- 与S450L组相比,H445Y组的干扰素γ和α通路中的基因组在H445Y组下调.
- 在H445Y组中证实了干扰素诱导基因 (例如BATF2,SERPING1) 的低表达,特别是在广泛的肺病变中.
结论:
- Mtb rpoB 突变和特定的亚系显著影响宿主免疫反应.
- 了解宿主-病原体相互作用对于制定对抗耐药结核病流行病的策略至关重要.
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