Microevolutionary analysis of Clostridium difficile genomes to investigate transmission.
Microevolutionary analysis of Clostridium difficile genomes to investigate transmission.
复制标题
DOI：
10.1186/gb-2012-13-12-r118
复制
发表时间：
2012-12-21
期刊：
影响因子：
12.3
通讯作者：
Harding RM
中科院分区：
文献类型：
--
作者：
Didelot X;Eyre DW;Cule M;Ip CL;Ansari MA;Griffiths D;Vaughan A;O'Connor L;Golubchik T;Batty EM;Piazza P;Wilson DJ;Bowden R;Donnelly PJ;Dingle KE;Wilcox M;Walker AS;Crook DW;Peto TE;Harding RM
艰难梭菌感染的控制是一项主要的国际医疗保健优先事项，但由于对这些细菌的传播流行病学了解有限，这一点受到了阻碍。然而，随着下一代测序的到来，细菌病原体的传播研究正在迅速转变。在这里，我们对牛津郡四年来486例艰难梭菌的全部基因组进行了测序。我们证明，我们可以估计回到细菌谱系共同祖先的时间，并有足够的分辨率来区分直接传播是否可信。时间深度是使用宿主内进化速率来推断的，基于连续分离的基因组，我们估计每个基因组每年有1.4个突变。研究发现，这类貌似合理的传播与在医院共享时间和空间的患者对高度相关。相反，通过常规分型匹配的绝大多数基因组对在一个月内从患者中分离出来，它们的亲缘关系太远，不能直接传播。我们的结果证实，有症状的艰难梭菌病例之间的医院传播对当前感染率的影响比人们普遍认为的要小得多，这阐明了未来研究其他传播途径的重要性，例如来自无症状携带者的传播。随着DNA测序成本的迅速下降和使用越来越广泛，基因组学将彻底改变我们对细菌病原体传播的理解。
The control of Clostridium difficile infection is a major international healthcare priority, hindered by a limited understanding of transmission epidemiology for these bacteria. However, transmission studies of bacterial pathogens are rapidly being transformed by the advent of next generation sequencing. Here we sequence whole C. difficile genomes from 486 cases arising over four years in Oxfordshire. We show that we can estimate the times back to common ancestors of bacterial lineages with sufficient resolution to distinguish whether direct transmission is plausible or not. Time depths were inferred using a within-host evolutionary rate that we estimated at 1.4 mutations per genome per year based on serially isolated genomes. The subset of plausible transmissions was found to be highly associated with pairs of patients sharing time and space in hospital. Conversely, the large majority of pairs of genomes matched by conventional typing and isolated from patients within a month of each other were too distantly related to be direct transmissions. Our results confirm that nosocomial transmission between symptomatic C. difficile cases contributes far less to current rates of infection than has been widely assumed, which clarifies the importance of future research into other transmission routes, such as from asymptomatic carriers. With the costs of DNA sequencing rapidly falling and its use becoming more and more widespread, genomics will revolutionize our understanding of the transmission of bacterial pathogens.