Linking the Resistome and Plasmidome to the Microbiome

The rapid spread of antibiotic resistance is a serious human health threat. A range of environments have been identified as reservoirs of the antibiotic resistance genes (ARGs) found in pathogens. However, we lack understanding of the origins of these ARGs and their spread from environment to clinic. This is partly due to our inability to identify the bacterial hosts of ARGs and the mobile genetic elements that mediate this spread, such as plasmids and integrons. Here we demonstrated that the in vivo proximity ligation method Hi-C can determine the in situ host range of ARGs, plasmids, and integrons in a wastewater sample by physically linking them to their host chromosomes. Hi-C detected both previously known and novel associations between ARGs, mobile elements and host genomes, mostly validating this method. A better identification of the natural carriers of ARGs will aid the development of strategies to limit resistance spread to pathogens.