Instituto de Biomedicina y Biotecnología de Cantabria, (CSIC, Universidad de Cantabria), Santander, Spain.
Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
mSystems. 2024 Aug 20;9(8):e0036524. doi: 10.1128/msystems.00365-24. Epub 2024 Jul 26.
Bacterial relatedness measured using select chromosomal loci forms the basis of public health genomic surveillance. While approximating vertical evolution through this approach has proven exceptionally valuable for understanding pathogen dynamics, it excludes a fundamental dimension of bacterial evolution-horizontal gene transfer. Incorporating the accessory genome is the logical remediation and has recently shown promise in expanding epidemiological resolution for enteric pathogens. Employing -mer-based Jaccard index analysis, and a novel genome length distance metric, we computed pangenome (i.e., core and accessory) relatedness for the globally important pathogen serotype Typhi (Typhi), and graphically express both vertical (homology-by-descent) and horizontal (homology-by-admixture) evolutionary relationships in a reticulate network of over 2,200 U.S. Typhi genomes. This analysis revealed non-random structure in the Typhi pangenome that is driven predominantly by the gain and loss of mobile genetic elements, confirming and expanding upon known epidemiological patterns, revealing novel plasmid dynamics, and identifying avenues for further genomic epidemiological exploration. With an eye to public health application, this work adds important biological context to the rapidly improving ways of analyzing bacterial genetic data and demonstrates the value of the accessory genome to infer pathogen epidemiology and evolution.IMPORTANCEGiven bacterial evolution occurs in both vertical and horizontal dimensions, inclusion of both core and accessory genetic material (i.e., the pangenome) is a logical step toward a more thorough understanding of pathogen dynamics. With an eye to public, and indeed, global health relevance, we couple contemporary tools for genomic analysis with decades of research on mobile genetic elements to demonstrate the value of the pangenome, known and unknown, annotated, and hypothetical, for stratification of serovar Typhi (Typhi) populations. We confirm and expand upon what is known about Typhi epidemiology, plasmids, and antimicrobial resistance dynamics, and offer new avenues of exploration to further deduce Typhi ecology and evolution, and ultimately to reduce the incidence of human disease.
基于选择染色体基因座来衡量细菌的亲缘关系是公共卫生基因组监测的基础。虽然通过这种方法近似于垂直进化对于理解病原体动态非常有价值，但它排除了细菌进化的一个基本维度——水平基因转移。纳入辅助基因组是合乎逻辑的补救措施，最近在扩展肠病原体的流行病学分辨率方面显示出了前景。我们采用 -mer 基 Jaccard 指数分析和一种新的基因组长度距离度量标准，计算了全球重要病原体 血清型 Typhi（Typhi）的泛基因组（即核心和辅助）亲缘关系，并以网状网络的形式直观地表达了垂直（同源性-衍生）和水平（同源性-混合）进化关系超过 2200 个美国 Typhi 基因组。这项分析揭示了 Typhi 泛基因组中的非随机结构，主要由移动遗传元件的获得和丢失驱动，证实并扩展了已知的流行病学模式，揭示了新的质粒动态，并确定了进一步进行基因组流行病学探索的途径。着眼于公共卫生应用，这项工作为分析细菌遗传数据的快速改进方法添加了重要的生物学背景，并证明了辅助基因组在推断病原体流行病学和进化方面的价值。
由于细菌进化发生在垂直和水平两个维度上，因此包括核心和辅助遗传物质（即泛基因组）是更全面地了解病原体动态的合乎逻辑的步骤。考虑到公共卫生，实际上是全球健康的相关性，我们将当代基因组分析工具与几十年来对移动遗传元件的研究相结合，展示了泛基因组（已知和未知、注释和假设）的价值，用于 Typhi 血清型（Typhi）种群的分层。我们证实并扩展了关于 Typhi 流行病学、质粒和抗生素耐药性动态的已知信息，并提供了新的探索途径，以进一步推断 Typhi 的生态和进化，并最终降低人类疾病的发病率。
