Tracking the horizontal transfer of plasmids inShigella sonneiandShigella flexneriusing phylogenetics

Abstract

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 ofShigella sonneiandShigella flexneriisolated 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 betweenS. sonneiandS. flexnerilineages, 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.

Phylodynamics Uncovers the Transmission of Antibiotic-ResistantEscherichia colibetween Canines and Humans in an Urban Environment

“…Similar plasmid profiles between local outbreak clusters inferred from chromosomal DNA suggest that at the time scales we are investigating, plasmids are largely maintained even during cross-species transmission. Using more isolates or explicitly tracking the movement of plasmids between different bacterial lineages could shine additional light into the cross-species transmission of E. coli (44). With relatively few host jumps captured by the genomic data, quantifying the rates of host jumps is complex.…”

“…MASCOT was then used jointly on all outbreak clusters inferring the effective population size of E. coli in humans and canines, the rates of transmission between them, and the rate of introduction of E. coli into either compartment. We assumed a rate of evolution of 4 SNP's per year, based on the rate estimate for Shigella sonnei from previous literature (44). As a site model, we used a GTR+Γ4 with estimated rates.…”