Lu Liu1,2, Yu Feng1,2, Alan McNally3, Zhiyong Zong1,2,4,5. 1. Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China. 2. Division of Infectious Diseases, State Key Laboratory of Biotherapy, Chengdu, China. 3. Institute of Microbiology and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. 4. Department of Infection Control, West China Hospital, Sichuan University, Chengdu, China. 5. Center for Pathogen Research, West China Hospital, Sichuan University, Chengdu, China.
Abstract
Objectives: New Delhi MBL (NDM) is a type of carbapenemase; 20 variants of NDM have been identified to date. We have found a new variant of NDM, NDM-21, and describe it here. Methods: A carbapenem-resistant Escherichia coli was subjected to WGS using an Illumina X10 sequencer to identify the antimicrobial resistance genes and its ST. The gene encoding the new variant of NDM was cloned into E. coli DH5α, with blaNDM-5 being cloned as the control. Transformants were tested for susceptibility to carbapenems. Mating was performed to obtain the plasmid carrying the new blaNDM gene and the complete plasmid sequence was obtained using long-read MinION sequencing. Results: The E. coli isolate belonged to ST617 and phylogenetic group A. It had a gene encoding NDM-21, a new NDM variant. NDM-21 differs from NDM-5 by a Gly-to-Ser amino acid substitution at position 69 (G69S). NDM-21 retains the same activity against carbapenems as NDM-5. blaNDM-21 is carried by a 46.1 kb IncX3 plasmid, which is self-transmissible, and is located in a complex genetic context as blaNDM-5. The isolate also carried blaCTX-M-55, which encodes an ESBL conferring resistance to aztreonam (which completed its resistance to all clinically available β-lactams), and rmtB, which mediates high-level resistance to aminoglycosides, on an IncFII plasmid. Conclusions: A new NDM variant has been identified and blaNDM-21 has evolved from blaNDM-5 on an IncX3 plasmid.
Objectives: New Delhi MBL (NDM) is a type of carbapenemase; 20 variants of NDM have been identified to date. We have found a new variant of NDM, NDM-21, and describe it here. Methods: A carbapenem-resistant Escherichia coli was subjected to WGS using an Illumina X10 sequencer to identify the antimicrobial resistance genes and its ST. The gene encoding the new variant of NDM was cloned into E. coli DH5α, with blaNDM-5 being cloned as the control. Transformants were tested for susceptibility to carbapenems. Mating was performed to obtain the plasmid carrying the new blaNDM gene and the complete plasmid sequence was obtained using long-read MinION sequencing. Results: The E. coli isolate belonged to ST617 and phylogenetic group A. It had a gene encoding NDM-21, a new NDM variant. NDM-21 differs from NDM-5 by a Gly-to-Ser amino acid substitution at position 69 (G69S). NDM-21 retains the same activity against carbapenems as NDM-5. blaNDM-21 is carried by a 46.1 kb IncX3 plasmid, which is self-transmissible, and is located in a complex genetic context as blaNDM-5. The isolate also carried blaCTX-M-55, which encodes an ESBL conferring resistance to aztreonam (which completed its resistance to all clinically available β-lactams), and rmtB, which mediates high-level resistance to aminoglycosides, on an IncFII plasmid. Conclusions: A new NDM variant has been identified and blaNDM-21 has evolved from blaNDM-5 on an IncX3 plasmid.
Authors: Allie Y Chen; Pei W Thomas; Zishuo Cheng; Nasa Y Xu; David L Tierney; Michael W Crowder; Walter Fast; Seth M Cohen Journal: ChemMedChem Date: 2019-05-24 Impact factor: 3.466
Authors: Zishuo Cheng; Christopher R Bethel; Pei W Thomas; Ben A Shurina; John-Paul Alao; Caitlyn A Thomas; Kundi Yang; Steven H Marshall; Huan Zhang; Aidan M Sturgill; Andrea N Kravats; Richard C Page; Walter Fast; Robert A Bonomo; Michael W Crowder Journal: Antimicrob Agents Chemother Date: 2021-03-18 Impact factor: 5.191