A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains.
A Genome-Wide Association Study to Identify Diagnostic Markers for Human Pathogenic Campylobacter jejuni Strains.
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DOI：
10.3389/fmicb.2017.01224
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发表时间：
2017
影响因子：
5.2
通讯作者：
Taboada EN
中科院分区：
文献类型：
--
作者：
Buchanan CJ;Webb AL;Mutschall SK;Kruczkiewicz P;Barker DOR;Hetman BM;Gannon VPJ;Abbott DW;Thomas JE;Inglis GD;Taboada EN
空肠弯曲杆菌是世界范围内主要的人类肠道病原体，尽管对其生物学、生态学和流行病学的理解有所提高，但用于鉴定可能引起疾病的菌株的工具有限。在目前的研究中，我们使用了一个数据库中的分型数据，该数据库代表了通过加拿大各种监测项目收集的24，000多个分离株，以确定166个来自流行C.用于全基因组测序的空肠亚型。序列数据被用于全基因组关联研究（GWAS），旨在确定与临床相关的C。空肠亚型。然后针对来自各种来源的大量（n = 3，902）临床相关和非临床相关基因组验证前瞻性标记物（n = 28）。共有25个基因，包括6组遗传连锁基因，被确定为临床相关的C。空肠亚型。虽然本研究中发现的一些基因先前已被证明在铁获得和维生素B5生物合成等重要过程中发挥作用，但其他基因的功能未知，或者是本研究所独有的，需要进一步研究。这些标记物中只有四种可以组合使用，以检测验证数据集中高达90%的临床相关分离株，并且这些标记物可以形成筛选测定的基础，以快速鉴定对公共卫生构成增加风险的菌株。目前的研究结果与C.感兴趣的空肠菌株通过特定辅助基因的存在来定义。
Campylobacter jejuni is a leading human enteric pathogen worldwide and despite an improved understanding of its biology, ecology, and epidemiology, limited tools exist for identifying strains that are likely to cause disease. In the current study, we used subtyping data in a database representing over 24,000 isolates collected through various surveillance projects in Canada to identify 166 representative genomes from prevalent C. jejuni subtypes for whole genome sequencing. The sequence data was used in a genome-wide association study (GWAS) aimed at identifying accessory gene markers associated with clinically related C. jejuni subtypes. Prospective markers (n = 28) were then validated against a large number (n = 3,902) of clinically associated and non-clinically associated genomes from a variety of sources. A total of 25 genes, including six sets of genetically linked genes, were identified as robust putative diagnostic markers for clinically related C. jejuni subtypes. Although some of the genes identified in this study have been previously shown to play a role in important processes such as iron acquisition and vitamin B5 biosynthesis, others have unknown function or are unique to the current study and warrant further investigation. As few as four of these markers could be used in combination to detect up to 90% of clinically associated isolates in the validation dataset, and such markers could form the basis for a screening assay to rapidly identify strains that pose an increased risk to public health. The results of the current study are consistent with the notion that specific groups of C. jejuni strains of interest are defined by the presence of specific accessory genes.