Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations
Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations
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DOI：
10.1371/journal.ppat.1003008
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发表时间：
2012-11-01
期刊：
影响因子：
6.7
通讯作者：
Kao, Rowland R.
中科院分区：
文献类型：
--
作者：
Biek, Roman;O'Hare, Anthony;Kao, Rowland R.
全基因组测序（WGS）技术作为细菌病原体的法医流行病学工具具有很大的前景。它可能是特别有用的研究所观察到的流行病的传播动力学，涉及一个很大程度上未抽样的“水库”主机，如牛结核病（bTB）在英国和爱尔兰的牛和獾。BTB是由牛分枝杆菌（Mycobacterium bovis）引起的。结核病复合体也包括人类结核病的病原体。在这项研究中，我们确定了一个时空连锁的26头牛和4只獾感染相同的可变数目串联重复序列（VNTR）型的M。牛序列之间的单核苷酸多态性（SNPs）确定的差异是一致的细菌谱系持续在农场或附近数年，尽管在此期间多次明确的全群测试。比较WGS数据的数学模型显示遗传分化和空间距离之间的良好相关性，但较差的对应网络的牛的运动或群内接触。獾分离株与最近的牛分离株显示出零至四个SNP差异，为最近两种宿主之间的传播提供了证据。这是M.牛瘟在农场的持续存在，多次爆发，并与当地獾持续不断地相互作用。然而，尽管分辨率前所未有，但现阶段无法推断传播的方向性。尽管感染时间和结核病采样时间之间的时间跨度通常很长，但我们的研究结果表明，即使没有详细的接触数据，仅WGS数据也可以提供对结核病流行病学的见解，并且更广泛的采样和分析将允许量化牛和獾之间传播的程度和方向。
Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled 'reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers.