| Title: |
Global dissemination of npmA mediated pan-aminoglycoside resistance via a mobile genetic element in Gram-positive bacteria |
| Authors: |
Serna,Carlos; Matamoros,Bosco R; Pulido-Vadillo,Mario; Delgado-Blas,Jose F; Jansen,Rogier R; Willems, Rob J L; Almeida,Alexandre; Harrison,Ewan M; Dupuy,Bruno; Coll,Francesc; Gonzalez-Zorn,Bruno; MMB-mcb; Infection & Immunity |
| Publication Year: |
2025 |
| Subject Terms: |
Aminoglycosides/pharmacology; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Clostridioides difficile/genetics; DNA Transposable Elements/genetics; Drug Resistance; Bacterial/genetics; Enterococcus faecium/genetics; Genome; Gram-Positive Bacteria/genetics; Humans; Interspersed Repetitive Sequences/genetics; Methyltransferases/genetics; Microbial Sensitivity Tests; General Chemistry; General Biochemistry,Genetics and Molecular Biology; General Physics and Astronomy; Journal Article |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/466957 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/466957 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.7FA09C77 |
| Database: |
BASE |