Antibiotic resistance genes are differentially mobilized according to resistance mechanism

Author:

Nielsen Tue Kjærgaard1ORCID,Browne Patrick Denis1ORCID,Hansen Lars Hestbjerg1ORCID

Affiliation:

1. Department of Plant and Environmental Sciences, Section for Environmental Microbiology and Biotechnology, University of Copenhagen , Thorvaldsensvej 40, Frederiksberg C 1871, Denmark

Abstract

Abstract Background Screening for antibiotic resistance genes (ARGs) in especially environmental samples with (meta)genomic sequencing is associated with false-positive predictions of phenotypic resistance. This stems from the fact that most acquired ARGs require being overexpressed before conferring resistance, which is often caused by decontextualization of putative ARGs by mobile genetic elements (MGEs). Consequent overexpression of ARGs can be caused by strong promoters often present in insertion sequence (IS) elements and integrons and the copy number effect of plasmids, which may contribute to high expression of accessory genes. Results 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. It is concluded that antibiotic efflux genes are rarely mobilized and 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. Conclusions In this study, ARGs in all complete bacterial genomes are classified by their association with MGEs, using the proposed ARG-MOB scale. 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. An interactive table of all results is provided for future studies targeting highly mobilized ARGs.

Publisher

Oxford University Press (OUP)

Subject

Computer Science Applications,Health Informatics

Reference98 articles.

1. A framework for identifying the recent origins of mobile antibiotic resistance genes;Ebmeyer;Communications Biol,2021

2. Call of the wild: antibiotic resistance genes in natural environments;Allen;Nat Rev Microbiol,2010

3. The role of natural environments in the evolution of resistance traits in pathogenic bacteria;Martinez;Proc R Soc B Biol Sci,2009

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