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Determining the role of acquired 16S rRNA methyltransferase NpmA in conferring aminoglycoside resistance

genomics
microbiology
infectious-diseases

Abstract

Background. The 16S rRNA methyltransferase, NpmA, and its variants are thought to act synergistically with co-localizing antibiotic resistance genes (ARGs) to confer high-level resistance to 4,5- and 4,6-disubstituted-2-deoxystreptamine class of aminoglycosides. However, the impact of NpmA as a sole and independent determinant of antibiotic resistance to the aminoglycosides remains to be evaluated.

Methods. E. coli TOP10 cells expressing NpmA were employed for growth assay in the presence of different concentrations of aminoglycosides, followed by detection of methylation-induced modification at A1408 using Oxford Nanopore Technology (ONT)-based direct RNA sequencing.

Results. NpmA independently confers high-level, targeted resistance to a broad range of aminoglycosides in vivo with no cross-resistance to other tested antibiotic classes, underscoring its high specificity and role in MDR evolution. Further, m 1 A1408 methylation, a key signature of NpmA activity, was identified using direct RNA sequencing, underscoring the use of this method for detecting AMR-associated RNA modifications.

Conclusions. The delineation of functional autonomy of 16S RMTase NpmA, independent of other resistance determinants and ARGs underscores the key role of this resistance feature, which must be considered to enable better clinical management of AMR with aminoglycosides.

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