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Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria

Author

Listed:
  • Carlos Serna

    (Complutense University of Madrid)

  • Bosco R. Matamoros

    (Complutense University of Madrid)

  • Mario Pulido-Vadillo

    (Complutense University of Madrid)

  • Jose F. Delgado-Blas

    (Complutense University of Madrid
    Institut Pasteur, Université Paris-Cité)

  • Rogier R. Jansen

    (Onze Lieve Vrouwe Gasthuis)

  • Rob J. L. Willems

    (University Medical Center Utrecht)

  • Alexandre Almeida

    (University of Cambridge)

  • Ewan M. Harrison

    (Wellcome Sanger Institute
    University of Cambridge)

  • Bruno Dupuy

    (Université Paris-Cité)

  • Francesc Coll

    (Wellcome Sanger Institute
    Institute of Biomedicine of Valencia (IBV-CSIC))

  • Bruno Gonzalez-Zorn

    (Complutense University of Madrid)

Abstract

The npmA gene, encoding a 16S rRNA methyltransferase, confers resistance to all clinically available aminoglycosides, posing a significant threat to effective antibiotic therapy. We analyze 1,932,812 bacterial genomes to investigate the distribution and mobilization of npmA variants. npmA is not found in Gram-negative bacteria, where it was originally described, but is identified among Gram-positive bacteria, predominantly as the npmA2 variant in the globally distributed Clostridioides difficile ST11 lineage. We also detect npmA2 in two vancomycin-resistant Enterococcus faecium isolates from a Dutch hospital. Upon sequencing and phenotypic analysis, we determine that E. faecium isolates are pan-resistant to aminoglycosides. Genomic characterization links npmA2 to a composite transposon, Tn7734, which is integrated within a previously uncharacterized Integrative and Conjugative Element (ICE) Tn7740, present in both npmA2-carrying C. difficile and E. faecium clinical isolates. Tn7740-like, but not npmA2, appears across diverse taxa, including human microbiome members. Here, we show that Tn7740 likely facilitates cross-species npmA2 mobilization between these Gram-positive bacteria and emphasize the risk of mobile genetic elements transferring pan-aminoglycoside resistance between clinically important bacterial pathogens.

Suggested Citation

  • Carlos Serna & Bosco R. Matamoros & Mario Pulido-Vadillo & Jose F. Delgado-Blas & Rogier R. Jansen & Rob J. L. Willems & Alexandre Almeida & Ewan M. Harrison & Bruno Dupuy & Francesc Coll & Bruno Gonz, 2025. "Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61152-y
    DOI: 10.1038/s41467-025-61152-y
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    References listed on IDEAS

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    1. Mislav Acman & Ruobing Wang & Lucy Dorp & Liam P. Shaw & Qi Wang & Nina Luhmann & Yuyao Yin & Shijun Sun & Hongbin Chen & Hui Wang & Francois Balloux, 2022. "Role of mobile genetic elements in the global dissemination of the carbapenem resistance gene blaNDM," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. repec:plo:pcbi00:1004041 is not listed on IDEAS
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