Satta Giovanni, Witney Adam A, Shorten Robert J, Karlikowska Magdalena, Lipman Marc, McHugh Timothy D
Department of Infection, Centre for Clinical Microbiology, University College London, London, UK.
Imperial College Healthcare NHS Trust, London, UK.
BMC Med. 2016 Aug 16;14(1):117. doi: 10.1186/s12916-016-0659-6.
The largest outbreak of isoniazid-resistant (INH-R) Mycobacterium tuberculosis in Western Europe is centred in North London, with over 400 cases diagnosed since 1995. In the current study, we evaluated the genetic variation in a subset of clinical samples from the outbreak with the hypothesis that these isolates have unique biological characteristics that have served to prolong the outbreak.
Fitness assays, mutation rate estimation, and whole-genome sequencing were performed to test for selective advantage and compensatory mutations.
This detailed analysis of the genetic variation of these INH-R samples suggests that this outbreak consists of successful, closely related, circulating strains with heterogeneous resistance profiles and little or no associated fitness cost or impact on their mutation rate.
Specific deletions and SNPs could be a peculiar feature of these INH-R M. tuberculosis isolates, and could potentially explain their persistence over the years.
西欧最大规模的耐异烟肼结核分枝杆菌疫情集中在伦敦北部，自1995年以来已诊断出400多例病例。在本研究中，我们评估了此次疫情中一部分临床样本的基因变异情况，假设这些分离株具有独特的生物学特性，从而导致疫情持续时间延长。
进行适应性测定、突变率估计和全基因组测序，以检测选择性优势和补偿性突变。
对这些耐异烟肼样本的基因变异进行的详细分析表明，此次疫情由成功的、密切相关的、具有不同耐药谱的流行菌株组成，几乎没有或完全没有相关的适应性代价，对其突变率也没有影响。
特定的缺失和单核苷酸多态性可能是这些耐异烟肼结核分枝杆菌分离株的一个特殊特征，并可能解释它们多年来的持续存在。
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