Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains

Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. He...

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Bibliographic Details
Main Authors: Apjok Gábor
Számel Mónika
Christodoulou Chryso
Seregi Viktória
Vásárhelyi Bálint Márk
Stirling Tamás
Sári Tóbiás
Nagrand Erika
Kovács Dorina
Szili Petra
Lantos Ildikó Ilona
Méhi Orsolya Katinka
Jangir Pramod Kumar
Herczeg Róbert
Gálik Bence
Gyenesei Attila
Draskovits Gábor
Nyerges Ákos
Fekete Gergely
Bodai László
Zsindely Nóra
Dénes Béla
Papp Balázs
Pál Csaba
Kintses Bálint
et al
Format: Article
Published: 2023
Series:NATURE MICROBIOLOGY 8 No. 3
Subjects:
doi:10.1038/s41564-023-01320-2

mtmt:33634821
Online Access:http://publicatio.bibl.u-szeged.hu/27235
Description
Summary:Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE). This approach combines and improves the use of T7 bacteriophage with exchanged tail fibres and targeted mutagenesis to expand phage host-specificity and efficiency for functional metagenomics. These modified phage particles were used to introduce large metagenomic plasmid libraries into clinically relevant bacterial pathogens. By screening for ARGs in soil and gut microbiomes and clinical genomes against 13 antibiotics, we demonstrate that this approach substantially expands the list of identified ARGs. Many ARGs have species-specific effects on resistance; they provide a high level of resistance in one bacterial species but yield very limited resistance in a related species. Finally, we identified mobile ARGs against antibiotics that are currently under clinical development or have recently been approved. Overall, DEEPMINE expands the functional metagenomics toolbox for studying microbial communities.
Physical Description:410-423
ISSN:2058-5276