Functional and Structural Characterization of Acquired 16S rRNA Methyltransferase NpmB1 Conferring Pan-Aminoglycoside Resistance

• Published in: Antimicrobial agents and chemotherapy Vol. 65; no. 10; p. e0100921
• Main Authors: Kawai, Akito, Suzuki, Masahiro, Tsukamoto, Kentaro, Minato, Yusuke, Doi, Yohei
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 17.09.2021
• Subjects: Aminoglycosides - pharmacology; Anti-Bacterial Agents - pharmacology; Antimicrobial Chemotherapy; Drug Resistance, Bacterial - genetics; Escherichia coli - genetics; Escherichia coli Proteins - genetics; Mechanisms of Resistance; Methyltransferases - genetics; Phylogeny; RNA, Ribosomal, 16S - genetics; aminoglycoside resistance; 16S rRNA; methyltransferase
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/aac.01009-21

Posttranslational methylation of the A site of 16S rRNA at position A1408 leads to pan-aminoglycoside resistance encompassing both 4,5- and 4,6-disubstituted 2-deoxystreptamine (DOS) aminoglycosides. To date, NpmA is the only acquired enzyme with such a function. Here, we present the function and structure of NpmB1, whose sequence was identified in Escherichia coli genomes registered from the United Kingdom. NpmB1 possesses 40% amino acid identity with NpmA1 and confers resistance to all clinically relevant aminoglycosides, including 4,5-DOS agents. Phylogenetic analysis of NpmB1 and NpmB2, its single-amino-acid variant, revealed that the encoding gene was likely acquired by E. coli from a soil bacterium. The structure of NpmB1 suggests that it requires a structural change of the β6/7 linker in order to bind to 16S rRNA. These findings establish NpmB1 and NpmB2 as the second group of acquired pan-aminoglycoside resistance 16S rRNA methyltransferases.