TY - JOUR
T1 - Functional and structural characterization of acquired 16s rRNA methyltransferase npmb1 conferring pan-aminoglycoside resistance
AU - Kawai, Akito
AU - Suzuki, Masahiro
AU - Tsukamoto, Kentaro
AU - Minato, Yusuke
AU - Doi, Yohei
N1 - Funding Information:
Synchrotron experiments were performed with the approval of the Photon Factory Program Advisory Committee (proposal no. 2019G592). We are grateful to the beamline staff for their support of our synchrotron experiments and to Meiji Seika Pharma Co., Ltd., for the provision of arbekacin.
Funding Information:
Y.D. was supported by grants R01AI104895, R21AI135522, and R21AI151362 from the National Institutes of Health.
Publisher Copyright:
Copyright © 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
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U2 - 10.1128/AAC.01009-21
DO - 10.1128/AAC.01009-21
M3 - Article
C2 - 34310216
AN - SCOPUS:85115189350
SN - 0066-4804
VL - 65
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 10
M1 - e01009-21
ER -