Functional and structural characterization of acquired 16s rRNA methyltransferase npmb1 conferring pan-aminoglycoside resistance

研究成果: Article査読

抄録

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 b6/7 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.

本文言語English
論文番号e01009-21
ジャーナルAntimicrobial agents and chemotherapy
65
10
DOI
出版ステータスPublished - 10-2021

All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬理学(医学)
  • 感染症

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