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

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 st...

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Published in:Antimicrobial agents and chemotherapy 2021-09, Vol.65 (10), p.e0100921-e0100921
Main Authors: Kawai, Akito, Suzuki, Masahiro, Tsukamoto, Kentaro, Minato, Yusuke, Doi, Yohei
Format: Article
Language:English
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
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Summary: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.
ISSN:0066-4804
1098-6596
DOI:10.1128/aac.01009-21