Extensive screening reveals previously undiscovered aminoglycoside resistance genes in human pathogens
Artikel i vetenskaplig tidskrift, 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.
Författare
David Lund
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
Roelof Dirk Coertze
Göteborgs universitet
Marcos Parras Moltó
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
Fanny Berglund
Göteborgs universitet
Carl-Fredrik Flach
Göteborgs universitet
Anna Johnning
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
Stiftelsen Fraunhofer-Chalmers Centrum för Industrimatematik
D. G.Joakim Larsson
Göteborgs universitet
Erik Kristiansson
Göteborgs universitet
Chalmers, Matematiska vetenskaper, Tillämpad matematik och statistik
Communications Biology
23993642 (eISSN)
Vol. 6 1 812Miljöns roll för utveckling och spridning av antibiotikaresistens
Vetenskapsrådet (VR) (2018-05771), 2019-01-01 -- 2024-12-31.
Nya resistensgener mot antibiotika och deras spridning i miljön
Vetenskapsrådet (VR) (2019-03482), 2020-01-01 -- 2023-12-31.
Ämneskategorier
Infektionsmedicin
Mikrobiologi
Mikrobiologi inom det medicinska området
DOI
10.1038/s42003-023-05174-6
PubMed
37537271