Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
PLoS Pathog. 2012 Sep;8(9):e1002874. doi: 10.1371/journal.ppat.1002874. Epub 2012 Sep 6.
Bacterial pathogens impose a heavy burden of disease on human populations worldwide. The gravest threats are posed by highly virulent respiratory pathogens, enteric pathogens, and HIV-associated infections. Tuberculosis alone is responsible for the deaths of 1.5 million people annually. Treatment options for bacterial pathogens are being steadily eroded by the evolution and spread of drug resistance. However, population-level whole genome sequencing offers new hope in the fight against pathogenic bacteria. By providing insights into bacterial evolution and disease etiology, these approaches pave the way for novel interventions and therapeutic targets. Sequencing populations of bacteria across the whole genome provides unprecedented resolution to investigate (i) within-host evolution, (ii) transmission history, and (iii) population structure. Moreover, advances in rapid benchtop sequencing herald a new era of real-time genomics in which sequencing and analysis can be deployed within hours in response to rapidly changing public health emergencies. The purpose of this review is to highlight the transformative effect of population genomics on bacteriology, and to consider the prospects for answering abiding questions such as why bacteria cause disease.
细菌病原体给全球人口带来了沉重的疾病负担。最严重的威胁来自高毒力的呼吸道病原体、肠道病原体和与 HIV 相关的感染。仅结核病每年就导致 150 万人死亡。由于耐药性的产生和传播,治疗细菌病原体的选择方案正在逐渐减少。然而,人群水平的全基因组测序为对抗致病菌带来了新的希望。通过深入了解细菌的进化和疾病的病因,这些方法为新的干预措施和治疗靶点铺平了道路。对整个基因组的细菌群体进行测序,为研究(i)体内进化、(ii)传播史和(iii)种群结构提供了前所未有的分辨率。此外,快速台式测序的进步预示着实时基因组学的新时代的到来,在这个时代,测序和分析可以在几个小时内部署,以应对迅速变化的突发公共卫生事件。本文的目的是强调群体基因组学对细菌学的变革性影响,并考虑回答一些持久问题的前景,例如为什么细菌会导致疾病。