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评估结核病临床分离物形成可行的但不复制的亚种群的倾向

Julian L Coetzee¹, Nastassja L Kriel², Johannes Loubser¹

¹DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg, Cape Town, 7505, South Africa.

Scientific reports

|November 12, 2024

概括

来自结核病治疗结果不成功的患者的Mycobacterium结核病临床分离物形成了比治愈的患者更大的持久性亚群. 这表明,结核病持续形成与结核病治疗成功率低下之间存在联系.

科学领域:

微生物学微生物学
传染性疾病传染性疾病
基因组学就是基因组学.

背景情况:

结核病 (TB) 治疗可能由于耐药性或表型耐药性而失败.
结核菌菌 (M.tb) 持续存在,是一种活力但不复制 (VBNR) 细菌的亚群,与结核病治疗失败有关.
在未接受过治疗的隔离体中研究M.tb持续形成可能会揭示治疗失败的机制.

研究的目的:

为了比较VBNR亚群组形成能力的药物敏感的M.tb从结核病患者的临床隔离与治愈患者的结核病患者没有成功的治疗结果.
为了确定与治疗失败孤立体中VBNR形成增加相关的潜在基因组差异.

主要方法:

收集了从结核病患者中获得的未经治疗的,对药物敏感的M.tb临床隔离物,这些结核病患者有记录的治疗结果 (未成功与治愈).
感染的THP-1巨细胞与VBNR M.tb亚群的分离物和定量百分比.
进行了表型和基因型药物敏感性测试.
在选定的分离物上进行全基因组测序.

主要成果:

来自结核病治疗结果不成功的患者的临床分离物形成了显著更大的VBNR M.tb亚群 (2.67-13.71%) 与治愈病例 (0-1.63%).
所有的分离物被证实对药物敏感.
全基因组测序确定了23个独特的非同义基因组变异在治疗失败的隔离物中,而不在治愈的隔离物中.

结论:

没有接受过治疗的M.tb临床分离体在VBNR亚群形成中表现出异质性.
形成VBNR M.tb亚群的更高倾向与结核病治疗不成功的结果有关.
基因组变异可能有助于在治疗失败的孤立体中观察到的VBNR形成的增加,这需要进一步调查.

关键词:

异质的异质的坚持不坚持不坚持,坚持不.这就是为什么TBTBTBTB 治疗失败的原因是治疗失败.结核病是一种疾病.这是一个VBNR.

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