TY - JOUR

T1 - Antibiotic resistance genes are differentially mobilized according to resistance mechanism

AU - Nielsen, Tue Kjærgaard

AU - Browne, Patrick Denis

AU - Hansen, Lars Hestbjerg

N1 - Publisher Copyright: © 2022 The Author(s). Published by Oxford University Press GigaScience.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - antibiotic resistance genes

KW - bioinformatics

KW - mobile genetic elements

U2 - 10.1093/gigascience/giac072

DO - 10.1093/gigascience/giac072

M3 - Journal article

C2 - 35906888

AN - SCOPUS:85135207500

VL - 11

JO - GigaScience

JF - GigaScience

SN - 2047-217X

M1 - giac072

ER -