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

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

  • Nat Microbiol. 2023 Feb 9. doi: 10.1038/s41564-023-01320-2.
Gábor Apjok # 1 2,  Mónika Számel # 1 2,  Chryso Christodoulou # 1,  Viktória Seregi 1 3,  Bálint Márk Vásárhelyi 1,  Tamás Stirling 1 2 4,  Bálint Eszenyi 1,  Tóbiás Sári 1 2,  Fanni Vidovics 1,  Erika Nagrand 1,  Dorina Kovács 1,  Petra Szili 1 5,  Ildikó Ilona Lantos 1,  Orsolya Méhi 1,  Pramod K Jangir 1 2 6,  Róbert Herczeg 7,  Bence Gálik 7 8,  Péter Urbán 7,  Attila Gyenesei 7 8,  Gábor Draskovits 1,  Ákos Nyerges 1,  Gergely Fekete 1,  László Bodai 9,  Nóra Zsindely 10,  Béla Dénes 11,  Ido Yosef 12,  Udi Qimron 12,  Balázs Papp 1 4 13,  Csaba Pál 14,  Bálint Kintses 15 16 17
Affiliations

Affiliations

  • 1 Synthetic and System Biology Unit, Institute of Biochemistry, Biological Research Centre, National Laboratory of Biotechnology, Eötvös Loránd Research Network (ELKH), Szeged, Hungary.
  • 2 Doctoral School of Biology, University of Szeged, Szeged, Hungary.
  • 3 HCEMM-BRC Translational Microbiology Research Group, Szeged, Hungary.
  • 4 Institute of Biochemistry, Biological Research Centre, National Laboratory for Health Security, Eötvös Loránd Research Network (ELKH), Szeged, Hungary.
  • 5 Doctoral School of Multidisciplinary Medical Sciences, University of Szeged, Szeged, Hungary.
  • 6 Department of Zoology, University of Oxford, Oxford, UK.
  • 7 Bioinformatics Research Group, Genomics and Bioinformatics Core Facility, Szentágothai Research Centre, University of Pécs, Pécs, Hungary.
  • 8 Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland.
  • 9 Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
  • 10 Department of Genetics, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
  • 11 Veterinary Diagnostic Directorate, National Food Chain Safety Office, Budapest, Hungary.
  • 12 Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • 13 HCEMM-BRC Metabolic Systems Biology Lab, Szeged, Hungary.
  • 14 Synthetic and System Biology Unit, Institute of Biochemistry, Biological Research Centre, National Laboratory of Biotechnology, Eötvös Loránd Research Network (ELKH), Szeged, Hungary. csaba.pal@brc.hu.
  • 15 Synthetic and System Biology Unit, Institute of Biochemistry, Biological Research Centre, National Laboratory of Biotechnology, Eötvös Loránd Research Network (ELKH), Szeged, Hungary. kintses.balint@brc.hu.
  • 16 HCEMM-BRC Translational Microbiology Research Group, Szeged, Hungary. kintses.balint@brc.hu.
  • 17 Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary. kintses.balint@brc.hu.
  • # Contributed equally.
PMID: 36759752 DOI: 10.1038/s41564-023-01320-2
Abstract

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.

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