SHIP: identifying antimicrobial resistance gene transfer between plasmids.

Abstract

Plasmids are carriers for antimicrobial resistance (AMR) genes and can exchange genetic material with other structures, contributing to the spread of AMR. There is no reliable approach to identify the transfer of AMR genes across plasmids. This is mainly due to the absence of a method to assess the phylogenetic distance of plasmids, as they show large DNA sequence variability. Identifying and quantifying such transfer can provide novel insight into the role of small mobile elements and resistant plasmid regions in the spread of AMR. We developed SHIP, a novel method to quantify plasmid similarity based on the dynamics of plasmid evolution. This allowed us to find conserved fragments containing AMR genes in structurally different and phylogenetically distant plasmids, which is evidence for lateral transfer. Our results show that regions carrying AMR genes are highly mobilizable between plasmids through transposons, integrons, and recombination events, and contribute to the spread of AMR. Identified transferred fragments include a multi-resistant complex class 1 integron in Escherichia coli and Klebsiella pneumoniae, and a region encoding tetracycline resistance transferred through recombination in Enterococcus faecalis. The code developed in this work is available at https://github.com/AbeelLab/plasmidHGT.