Outhred Alexander C, Gurjav Ulziijargal, Jelfs Peter, McCallum Nadine, Wang Qinning, Hill-Cawthorne Grant A, Marais Ben J, Sintchenko Vitali
Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Sydney, NSW, Australia.
Children's Hospital at Westmead, Sydney, NSW, Australia.
Front Public Health. 2020 Aug 27;8:455. doi: 10.3389/fpubh.2020.00455. eCollection 2020.
More human deaths have been attributable to than any other pathogen, and the epidemic is sustained by ongoing transmission. Various typing schemes have been developed to identify strain-specific differences and track transmission dynamics in affected communities, with recent introduction of whole genome sequencing providing the most accurate assessment. Mycobacterial interspersed repetitive unit (MIRU) typing is a family of variable number tandem repeat schemes that have been widely used to study the molecular epidemiology of . MIRU typing was used in most well-resourced settings to perform routine molecular epidemiology. Instances of MIRU homoplasy have been observed in comparison with sequence-based phylogenies, limiting its discriminatory value. A fundamental question is whether the observed homoplasy arises purely through stochastic processes, or whether there is evidence of natural selection. We compared repeat numbers at 24 MIRU loci with a whole genome sequence-based phylogeny of 245 isolates representing three modern lineages. This analysis demonstrated extensive homoplasy of repeat numbers, but did not detect any evidence of natural selection of repeat numbers, at least since the ancestral branching of the three modern lineages of . In addition, we observed good sensitivity but poor specificity and positive predictive values of MIRU-24 to detect clusters of recent transmission, as defined by whole-genome single nucleotide polymorphism analysis. These findings provide mechanistic insight, and support a transition away from VNTR-based typing toward sequence-based typing schemes for both research and public health purposes.
与任何其他病原体相比，由[病原体名称未给出]导致的人类死亡更多，且该流行病通过持续传播得以延续。已开发出各种分型方案来识别菌株特异性差异并追踪受影响社区的传播动态，最近引入的全基因组测序提供了最准确的评估。分枝杆菌散布重复单位（MIRU）分型是一类可变数目串联重复方案，已被广泛用于研究[病原体名称未给出]的分子流行病学。在大多数资源充足的环境中，MIRU分型被用于进行常规分子流行病学研究。与基于序列的系统发育相比，已观察到MIRU同塑性的实例，这限制了其鉴别价值。一个基本问题是，观察到的同塑性是纯粹通过随机过程产生的，还是有自然选择的证据。我们将24个MIRU位点的重复数与基于全基因组序列的245株分离株的系统发育进行了比较，这些分离株代表了三个现代[病原体名称未给出]谱系。该分析表明重复数存在广泛的同塑性，但未检测到重复数自然选择的任何证据，至少自[病原体名称未给出]三个现代谱系的祖先分支以来没有。此外，我们观察到MIRU - 24检测近期传播簇的敏感性良好，但特异性和阳性预测值较差，近期传播簇由全基因组单核苷酸多态性分析定义。这些发现提供了机制性见解，并支持从基于可变数目串联重复序列的分型向基于序列的分型方案转变，以用于研究和公共卫生目的。
