NpmC, a novel A1408 16S rRNA methyltransferase in the gut of humans and animals
International Journal of Antimicrobial Agents publish this investigation article
November 8th, 2024
16S rRNA methyltransferases that act on residue A1408, NpmA and NpmB, confer high-level resistance to virtually all the aminoglycosides, but their reports are scarce. Analysing metagenomic projects in a One Health context, we identified in human and animal gut microbiomes from China and Canada a novel gene, npmC, that shares an identity of 91.5% with npmA, and up to 92.7% at amino acidic level. The protein encoded by this gene presents the conserved motifs required for A1408 methylation. Expression of the gene resulted in high-level of resistance to 4,5-disubstituted 2-deoxystreptamine (2-DOS) and to 4-monosubstituted 2-DOS aminoglycosides, as well as a moderate resistance to 4,6-disusbstituted 2-DOS aminoglycosides, including the last resort aminoglycoside plazomicin. Methylation at residue A1408 was further confirmed by mass spectrometry assays. The analysis of the npmC gene background revealed that its genetic context is associated to different insertion sequences that could mobilise it. Similarities in the genetic context between npmC and npmA suggest that they share a common ancestor. The immediate genetic context of this methyltransferase suggests high relationship to the Eubacteriales order. This finding enlarges the list of the true pan-aminoglycoside 16S rRNA methyltransferases, that threaten the usefulness and development of next-generation aminoglycosides
Matamoros BR., Serna-Bernaldo C., Wedel E., Montero N., Kirpekar F. and Gonzalez-Zorn B..
 | Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
| Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
 | Department of Biochemistry and Molecular Biology. University of Southern Denmark (SDU). |
