Tracking the horizontal transfer of plasmids in Shigella sonnei and Shigella flexneri using phylogenetics

There is an urgent need for novel methods to track the emergence and dissemination of antimicrobial resistance (AMR) mechanisms that give rise to multi- and extensively-drug resistant bacterial pathogens. AMR mechanisms are most commonly associated with AMR genes that are carried on mobile elements, such as plasmids. Plasmids may move between lineages of the same or different bacterial species and thus Understanding when and where they were introduced into a population, as well as their persistence, is crucial to understanding the changing AMR dynamics in bacterial pathogens. Here we introduce an approach that allows us to reconstruct how plasmids move between bacterial lineages. To do so, we model the co-divergence of chromosomal and plasmid DNA in a Bayesian phylogenetic network approach using a joint coalescent and plasmid transfer process. We apply this new approach to a five year dataset of Shigella sonnei and Shigella flexneri isolated in Melbourne, Australia, reconstructing how different plasmids move within and between these species. Specifically, we investigate the long term co-divergence of the virulence plasmid, the gain and loss of small plasmids, and the recent acquisition and dissemination of the multidrug resistant (MDR) plasmid moving between S. sonnei and S. flexneri lineages, through multiple introductions from sampled and also unsampled sources. This approach has applications to both emerging and known bacterial pathogens and improves our understanding of where AMR-carrying plasmids are introduced and maintained in bacterial pathogens of human health importance. Our novel approach is implemented in the widely used BEAST2 software.