Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria
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 i...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61152-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849764095294701568 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Carlos Serna |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0d29d74b7b8a4dcea623a54aa9647a26 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0d29d74b7b8a4dcea623a54aa9647a262025-08-20T03:05:14ZengNature PortfolioNature Communications2041-17232025-07-0116111310.1038/s41467-025-61152-yGlobal dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteriaCarlos Serna0Bosco R. Matamoros1Mario Pulido-Vadillo2Jose F. Delgado-Blas3Rogier R. Jansen4Rob J. L. Willems5Alexandre Almeida6Ewan M. Harrison7Bruno Dupuy8Francesc Coll9Bruno Gonzalez-Zorn10Antimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of MadridAntimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of MadridAntimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of MadridAntimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of MadridDepartment of Medical Microbiology, Onze Lieve Vrouwe GasthuisDepartment of Medical Microbiology, University Medical Center UtrechtDepartment of Veterinary Medicine, University of CambridgeParasites and Microbes Programme, Wellcome Sanger InstitutePathogenesis of Bacterial Anaerobes Laboratory, Department of Microbiology, Institut Pasteur, Université Paris-CitéParasites and Microbes Programme, Wellcome Sanger InstituteAntimicrobial Resistance Unit (ARU), Animal Health Department, Faculty of Veterinary Medicine and VISAVET Health Surveillance Centre, Complutense University of MadridAbstract 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.https://doi.org/10.1038/s41467-025-61152-y |
| spellingShingle | 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 Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria Nature Communications |
| title | Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| title_full | Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| title_fullStr | Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| title_full_unstemmed | Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| title_short | Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| title_sort | global dissemination of npma mediated pan aminoglycoside resistance via a mobile genetic element in gram positive bacteria |
| url | https://doi.org/10.1038/s41467-025-61152-y |
| work_keys_str_mv | AT carlosserna globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT boscormatamoros globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT mariopulidovadillo globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT josefdelgadoblas globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT rogierrjansen globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT robjlwillems globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT alexandrealmeida globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT ewanmharrison globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT brunodupuy globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT francesccoll globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria AT brunogonzalezzorn globaldisseminationofnpmamediatedpanaminoglycosideresistanceviaamobilegeneticelementingrampositivebacteria |