Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva, Israel.
Epidemiology and Surveillance Support Unit, University of Lyon, French Agency for Food, Environmental and Occupational Health and Safety (ANSES), Lyon, France.
ISME J. 2023 May;17(5):649-659. doi: 10.1038/s41396-023-01373-5. Epub 2023 Feb 9.
Antimicrobial resistance (AMR) is a significant threat to public health. Plasmids are principal vectors of AMR genes, significantly contributing to their spread and mobility across hosts. Nevertheless, little is known about the dynamics of plasmid genetic exchange across animal hosts. Here, we use theory and methodology from network and disease ecology to investigate the potential of gene transmission between plasmids using a data set of 21 plasmidomes from a single dairy cow population. We constructed a multilayer network based on pairwise plasmid genetic similarity. Genetic similarity is a signature of past genetic exchange that can aid in identifying potential routes and mechanisms of gene transmission within and between cows. Links between cows dominated the transmission network, and plasmids containing mobility genes were more connected. Modularity analysis revealed a network cluster where all plasmids contained a mobM gene, and one where all plasmids contained a beta-lactamase gene. Cows that contain both clusters also share transmission pathways with many other cows, making them candidates for super-spreading. In support, we found signatures of gene super-spreading in which a few plasmids and cows are responsible for most gene exchange. An agent-based transmission model showed that a new gene invading the cow population will likely reach all cows. Finally, we showed that edge weights contain a non-random signature for the mechanisms of gene transmission, allowing us to differentiate between dispersal and genetic exchange. These results provide insights into how genes, including those providing AMR, spread across animal hosts.
抗微生物药物耐药性（AMR）对公共卫生构成重大威胁。质粒是 AMR 基因的主要载体，极大地促进了它们在宿主间的传播和转移。然而，我们对于动物宿主间质粒遗传交换的动态变化却知之甚少。在这里，我们使用来自网络和疾病生态学的理论和方法，利用从单个奶牛群体中获得的 21 个质粒组数据集，调查基因在质粒间传递的潜力。我们构建了一个基于质粒间遗传相似性的双层网络。遗传相似性是过去遗传交换的标志，有助于识别奶牛个体内和个体间基因传递的潜在途径和机制。奶牛间的联系在传播网络中占据主导地位，而含有移动基因的质粒则具有更高的连接性。模块性分析揭示了一个网络簇，其中所有质粒都含有一个 mobM 基因，另一个网络簇中所有质粒都含有一个β-内酰胺酶基因。同时含有这两个簇的奶牛也与许多其他奶牛共享传播途径，使它们成为超级传播者的候选者。实际上，我们发现了基因超级传播的特征，少数质粒和奶牛负责了大部分基因交换。基于主体的传播模型表明，一个新的基因入侵奶牛种群后，可能会传播到所有奶牛身上。最后，我们表明，边的权重包含基因传播机制的非随机特征，使我们能够区分扩散和遗传交换。这些结果为我们了解包括提供 AMR 的基因在内的基因如何在动物宿主间传播提供了新的见解。
