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在卢旺达的Mycobacterium tuberculosis菌株中产生了对利芬辛耐药性的突变

Isabel Cuella-Martin¹, Jean Claude Semuto Ngabonziza², Gabriela Torrea¹

¹Department of Biomedical Sciences, Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium.

International journal of mycobacteriology

|September 18, 2023

概括

利芬辛耐药结核病 (RR-TB) 的快速诊断正在改善,但可能会错过一些突变. 这项研究追踪了卢旺达30年的rpoB突变,揭示了随着诊断工具的转变而发生的多样性变化.

科学领域:

微生物学微生物学
遗传学遗传学是一种遗传学.
公共卫生公共卫生

背景情况:

目前世界卫生组织认可的针对抗利法素结核病 (RR-TB) 的测定可能错过了关键的rpoB突变.
完整的rpoB基因测序是参考标准,但在特有环境中通常无法使用.
在许多RR-TB环境中,rpoB突变的多样性和趋势在很大程度上是未知的.

研究的目的:

分析rpoB突变的多样性和趋势,在结核病分离物中赋予里法辛耐药性.
评估诊断工具发展对检测RR-TB赋予突变的影响.
评估边界和非热点rpoB突变的临床相关性.

主要方法:

对30年 (1991-2021) 期间在卢旺达收集的RR-TB分离物的rpoB序列数据的回顾性分析.
与从表型 (pDST) 转向基因型药物敏感性测试 (gDST) 的转变相关的突变流行率和多样性的比较.
研究特定突变,艾滋病毒状态和补偿突变之间的关联.

主要成果:

在540个被测序的RR-TB分离物中,419个 (77.6%) 具有确定的抗性突变,其中Ser450Leu占主导地位.
不被快速gDST覆盖的Val170Phe突变是罕见的.
像Asp435Tyr这样的边界突变随着快速gDST的采用而增加,并且与补偿突变的相关性较小.

结论:

在RR-TB突变多样性的变化与快速gDST的过渡相关,突出诊断工具的影响.
快速分子诊断可以减少在检测边界rpoB突变时的表型偏差.
对于在标准的 rifampicin 耐药性决定区域之外的突变保持持续警至关重要.

关键词:

边界突变是一种边界突变.卢旺达卢旺达卢旺达卢旺达卢旺达卢旺达卢旺达卢旺达卢旺达血清450 Leu Leu 的使用情况转移基因突变对利芬胺素产生抗性.rpoBB 的时间.

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