序列性Mycobacterium结核病菌的基因型-表型表征 在Bedaquiline耐药结核病中分离出来的结核病菌
Tyler S Brown1,2, Linrui Tang3, Shaheed Vally Omar4,5
1Section of Infectious Diseases, Boston University School of Medicine, Boston, Massachusetts, USA.
概括
药物耐药结核病 (DRTB) 中新兴的贝达基林耐药性是一个重大问题. 研究表明,耐药性可以在治疗期间获得或传播,强调需要更好的诊断和监测.
科学领域:
- 微生物学 微生物学
- 基因组学就是基因组学.
- 传染性疾病 传染性疾病
背景情况:
- 在Mycobacterium结核病 (Mtb) 中的Bedaquiline (BDQ) 耐药性威胁着耐药结核病 (DRTB) 治疗进展.
- 了解BDQ耐药性的出现对于有效的DRTB管理至关重要.
研究的目的:
- 描述BDQ耐药性的遗传基础和起源,从接受基于BDQ的治疗的患者中分离Mtb.
- 调查是否在治疗期间或由于先前存在的菌株而获得耐药性,包括传播.
主要方法:
- 用MGIT方法测量了Mtb分离物的BDQ最小抑制度 (MIC).
- 进行了全基因组测序,对来自BDQ MICs升高的参与者的串行Mtb分离物进行了测序.
主要成果:
- 大多数参与者 (16/24) 患有BDQ耐药结核病 (MIC ≥4μg/mL),其中8/24具有中等耐药性 (MIC = 2μg/mL).
- 预先存在的耐药性比治疗期间获得的耐药性更为常见;在8/24名参与者中观察到多克隆感染.
- BDQ耐药性涉及Rv0678的多种突变,参与者之间的基因相似隔离物表明了耐药菌株的潜在传播.
结论:
- 耐BDQ结核病通过各种机制出现,包括传输具有先前存在的抗药性菌株.
- 鉴定宿主内部的mtb多样性对于改善DRTB的诊断,监测和分子测试开发至关重要.
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