Extensive screening reveals previously undiscovered aminoglycoside resistance genes in human pathogens
Journal article, 2023
Antibiotic resistance is a growing threat to human health, caused in part by pathogens accumulating antibiotic resistance genes (ARGs) through horizontal gene transfer. New ARGs are typically not recognized until they have become widely disseminated, which limits our ability to reduce their spread. In this study, we use large-scale computational screening of bacterial genomes to identify previously undiscovered mobile ARGs in pathogens. From ~1 million genomes, we predict 1,071,815 genes encoding 34,053 unique aminoglycoside-modifying enzymes (AMEs). These cluster into 7,612 families (<70% amino acid identity) of which 88 are previously described. Fifty new AME families are associated with mobile genetic elements and pathogenic hosts. From these, 24 of 28 experimentally tested AMEs confer resistance to aminoglycoside(s) in Escherichia coli, with 17 providing resistance above clinical breakpoints. This study greatly expands the range of clinically relevant aminoglycoside resistance determinants and demonstrates that computational methods enable early discovery of potentially emerging ARGs.
Author
David Lund
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Roelof Dirk Coertze
University of Gothenburg
Marcos Parras Moltó
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Fanny Berglund
University of Gothenburg
Carl-Fredrik Flach
University of Gothenburg
Anna Johnning
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Fraunhofer-Chalmers Centre
D. G.Joakim Larsson
University of Gothenburg
Erik Kristiansson
University of Gothenburg
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
Communications Biology
23993642 (eISSN)
Vol. 6 1 812The Environment as a Driver of Antibiotic Resistance (EDAR)
Swedish Research Council (VR) (2018-05771), 2019-01-01 -- 2024-12-31.
The diversity and mobility of novel antibiotic resistance genes
Swedish Research Council (VR) (2019-03482), 2020-01-01 -- 2023-12-31.
Subject Categories
Infectious Medicine
Microbiology
Microbiology in the medical area
DOI
10.1038/s42003-023-05174-6
PubMed
37537271