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

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 () and Bruno Gonzalez-Zorn ()
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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
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
Bruno Dupuy: Université Paris-Cité
Francesc Coll: Wellcome Sanger Institute
Bruno Gonzalez-Zorn: Complutense University of Madrid

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61152-y

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