Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Microb Genom. 2022 Dec;8(12). doi: 10.1099/mgen.0.000906.
The White-Kauffmann-Le Minor (WKL) scheme is the most widely used typing scheme for reporting the disease prevalence of the enteric pathogen. With the advent of whole-genome sequencing (WGS), methods have increasingly replaced traditional serotyping due to reproducibility, speed and coverage. However, despite integrating genomic-based typing by serotyping tools such as SISTR, serotyping in certain contexts remains ambiguous and insufficiently informative. Specifically, serotyping does not attempt to resolve polyphyly. Furthermore, in spite of the widespread acknowledgement of polyphyly from genomic studies, the prevalence of polyphyletic serovars is not well characterized. Here, we applied a genomics approach to acquire the necessary resolution to classify genetically discordant serovars and propose an alternative typing scheme that consistently reflect natural populations. By accessing the unprecedented volume of bacterial genomic data publicly available in GenomeTrakr and PubMLST databases (>180 000 genomes representing 723 serovars), we characterized the global population structure and systematically identified putative non-monophyletic serovars. The proportion of putative non-monophyletic serovars was estimated higher than previous reports, reinforcing the inability of antigenic determinants to depict the complexity of evolutionary history. We explored the extent of genetic diversity masked by serotyping labels and found significant intra-serovar molecular differences across many clinically important serovars. To avoid false discovery due to incorrect serotyping calls, we cross-referenced reported serovar labels and concluded a low error rate in serotyping. The combined application of clustering statistics and genome-wide association methods demonstrated effective characterization of stable bacterial populations and explained functional differences. The collective methods adopted in our study have practical values in establishing genomic-based typing nomenclatures for an entire microbial species or closely related subpopulations. Ultimately, we foresee an improved typing scheme to be a hybrid that integrates both genomic and antigenic information such that the resolution from WGS is leveraged to improve the precision of subpopulation classification while preserving the common names defined by the WKL scheme.
白-考夫曼-莱蒙（WKL）方案是报告肠道病原体疾病流行率最广泛使用的分型方案。随着全基因组测序（WGS）的出现，由于可重复性、速度和覆盖范围，方法已越来越多地取代传统的血清分型。然而，尽管整合了基于基因组的分型，例如 SISTR 等血清分型工具，但在某些情况下血清分型仍然模糊不清且信息量不足。具体来说，血清分型并不试图解决多系性。此外，尽管基因组研究广泛承认多系性，但多系性血清型的流行情况尚未得到很好的描述。在这里，我们应用基因组学方法获得必要的分辨率来分类遗传上不一致的血清型，并提出一种替代的分型方案，该方案始终如一地反映自然种群。通过访问在 GenomeTrakr 和 PubMLST 数据库中公开提供的前所未有的细菌基因组数据集（>180000 个代表 723 个血清型的基因组），我们描述了全球种群结构，并系统地识别了可能的非单系血清型。非单系血清型的比例估计高于以前的报告，这进一步证实了抗原决定簇无法描绘进化历史的复杂性。我们探索了血清分型标签掩盖的遗传多样性程度，并在许多临床重要的血清型中发现了明显的血清内分子差异。为了避免因血清型分类错误而导致的假发现，我们交叉引用了报告的血清型标签，并得出血清型分类的错误率较低的结论。聚类统计和全基因组关联方法的综合应用证明了对稳定细菌种群的有效描述，并解释了功能差异。我们研究中采用的综合方法在建立整个微生物物种或密切相关的亚种群的基于基因组的分型命名法方面具有实用价值。最终，我们预计改进的分型方案将是一种混合方案，该方案将整合基因组和抗原信息，以便利用 WGS 的分辨率提高亚群分类的精度，同时保留 WKL 方案定义的通用名称。
