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Publications

Journal Article Epublish

PubMed: 40675954 DOI: 10.1038/s41467-025-61152-y

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

Nat Commun 16(1):6360

Authors: 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 Gonzalez-Zorn

Affiliations

  • Antimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of Madrid, Madrid, Spain.
  • Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur, Université Paris-Cité, Paris, France.
  • Department of Medical Microbiology, Onze Lieve Vrouwe Gasthuis, Amsterdam, Netherlands.
  • Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands.
  • Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.
  • Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
  • Department of Medicine, University of Cambridge, Cambridge, UK.
  • Pathogenesis of Bacterial Anaerobes Laboratory, Department of Microbiology, Institut Pasteur, Université Paris-Cité, Paris, France.
  • Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK.
  • Applied Microbial Genomics Unit, Department of Molecular Basis of Disease, Institute of Biomedicine of Valencia (IBV-CSIC), Valencia, Spain.
  • Antimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of Madrid, Madrid, Spain.

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.

MeSH

Genes, Gram-Positive Bacteria, Aminoglycosides, Bacteria