与获得的表型耐药性及其在结核病治疗期间的补偿演变相关的遗传因素
Guoqin Zhang1, Xianhui Sun2, Joy Fleming3
1Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Tianjin Center for Tuberculosis Control, Tianjin, China; University of Chinese Academy of Sciences, Beijing, China.
概括
结核病的抗菌素耐药性在药物压力下演变,在耐药性被检测到之前出现突变. 全基因组测序有助于早期检测和治疗调整.
科学领域:
- 微生物学 微生物学
- 遗传学 是一个遗传学.
- 传染性疾病 传染性疾病
背景情况:
- 在Mycobacterium结核病 (MTB) 中的抗菌素耐药性 (AMR) 对结核病 (TB) 治疗构成重大挑战.
- 了解AMR的演变和补偿机制对于有效的治疗策略至关重要.
研究的目的:
- 阐明MTB单独体中AMR的因素,演变和补偿.
- 调查宿主环境和抗结核药物的双重压力下的宿主内抗药性演变.
主要方法:
- 对337名肺结核患者进行了回顾性病例控制研究.
- 在多个时间点进行表型药物敏感性测试.
- 149个连续MTB分离的46名患者的全基因组测序 (WGS).
主要成果:
- 结核病治疗中断≥30天与获得的对异化 (INH) 和利芬素 (RIF) 的耐药性有关.
- 在双重压力下,MTB以每年每基因组1.2个单核酸多态的速度进化.
- 在出现INH和RIF的表型耐药性之前,已经检测到了AMR相关的突变.
结论:
- 补偿进化可能促进抗性突变的固定,影响表型AMR.
- 在临床上,WGS对于早期识别再感染和AMR获得具有重要意义.
- 结核病治疗应以基因测序为指导,特别是持久的阳性培养.
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