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<p>The <i>npmA</i> 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 <i>npmA</i> variants. <i>npmA</i> is not found in Gram-negative bacteria, where it was originally described, but is identified among Gram-positive bacteria, predominantly as the <i>npmA2</i> variant in the globally distributed <i>Clostridioides difficile</i> ST11 lineage. We also detect <i>npmA2</i> in two vancomycin-resistant <i>Enterococcus faecium</i> isolates from a Dutch hospital. Upon sequencing and phenotypic analysis, we determine that <i>E. faecium</i> isolates are pan-resistant to aminoglycosides. Genomic characterization links <i>npmA2</i> to a composite transposon, Tn<i>7734</i>, which is integrated within a previously uncharacterized Integrative and Conjugative Element (ICE) Tn<i>7740</i>, present in both <i>npmA2</i>-carrying <i>C. difficile</i> and <i>E. faecium</i> clinical isolates. Tn<i>7740</i>-like, but not <i>npmA2</i>, appears across diverse taxa, including human microbiome members. Here, we show that Tn<i>7740</i> likely facilitates cross-species <i>npmA2</i> mobilization between these Gram-positive bacteria and emphasize the risk of mobile genetic elements transferring pan-aminoglycoside resistance between clinically important bacterial pathogens.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • 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

摘要

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.