Multilayer Networks of Plasmid Genetic Similarity Reveal Potential Pathways of Gene Transmission

Abstract

Antimicrobial resistance (AMR) is a major threat to public health. Plasmids are principal vectors of antimicrobial resistance genes, greatly contributing to their spread and mobility across hosts. Nevertheless little is known about the dynamics of plasmid genetic exchange across animal hosts. The cow rumen ecosystem is an excellent model system because it hosts diverse plasmid communities which interact and exchange genes. 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 genetic similarity between plasmids serving as a signature for past genetic exchange to identify potential routes and mechanisms of gene transmission within and between cows. The transmission network was dominated by links between cows. Modularity analysis unraveled a major cross-cow transmission pathway with additional small pathways. Plasmid functions influenced network structure: plasmids containing mobility genes were more connected; those with the same AMR genes formed their own modules. We find signatures of gene superspreading 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 is likely to reach all cows. Finally, we showed that link 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 the mechanisms by which genes, including those providing AMR, spread across animal hosts.