Tracking pathogenetic bacteria at the plasmid, genome, and pan-genomic level.*

The rapid global increase of multidrug-resistant organisms presents a major global health threat that will dramatically reduce the efficacy of antibiotics and thus constrain the number of effective treatments available to patients. As opposed to analogous efforts in viral epidemiology, accurate reconstruction of the pandemic spread of antibiotic resistance remains intractable for reasonable sample sizes due, in large part, to the high rate of homologous recombination and horizontal gene transfer that prevents the application of traditional phylogenetic approaches. Lastly, complete assemblies are a prerequisite to such quantitative study.

In this talk, I will present a novel computational framework for bacterial evolution that generalizes the traditional linear reference genome to a pan-genomic non-planar graph. Using this framework, I will analyze 120 antibiotic resistant genomes collected in Basel, Switzerland over the course of a decade, sequenced with both ONT and Illumina data. We show that the evolution of antibiotic resistance exhibits a nested doll structure in which genetic transposition, homologous recombination, and clonal expansion occur at similar time-scales.