Mobilization of antibiotic resistance genes differ by resistance mechanism

Abstract

The degree to which antibiotic resistance genes (ARGs) are mobilized by insertion sequence (IS) elements, plasmids, and integrons has a strong association with their likelihood to function as resistance determinants. This stems from genetic decontextualization where strong promoters often present in IS elements and integrons and the copy number effect of plasmids contribute to high expression of accessory genes. Here, we screen all complete bacterial RefSeq genomes for ARGs. The genetic contexts of detected ARGs are investigated for IS elements, integrons, plasmids, and phylogenetic dispersion. The ARG-MOB scale is proposed which indicates how mobilized detected ARGs are in bacterial genomes. Antibiotic efflux genes are rarely mobilized and it is concluded that these are often housekeeping genes that are not decontextualized to confer resistance through overexpression. Even 80% of β-lactamases have never, or very rarely, been mobilized in the 15,790 studied genomes. However, some ARGs are indeed mobilized and co-occur with IS elements, plasmids, and integrons. These results have consequences for the design and interpretation of studies screening for resistance determinants, as mobilized ARGs pose a more concrete risk to human health, especially under heterologous expression, than groups of ARGs that have only been shown to confer resistance in cloning experiments.