title: Plasmid-Mediated NovelblaNDM-17Gene Encoding a Carbapenemase with Enhanced Activity in a Sequence Type 48 Escherichia coli Strain.
abstract: Carbapenem-resistantEnterobacteriaceae(CRE) have spread worldwide, leaving very few treatment options available. New Delhi metallo-beta-lactamase (NDM) is the main carbapenemase mediating CRE resistance and is of increasing concern. NDM-positiveEnterobacteriaceaeof human origin are frequently identified; however, the emergence of NDM, and particularly novel variants, in bacteria of food animal origin has never been reported. Here, we characterize a novel NDM variant (assigned NDM-17) identified in a β-lactam-resistant sequence type 48 (ST48)Escherichia colistrain that was isolated from a chicken in China. Compared to NDM-1, NDM-17 had three amino acid substitutions (V88L, M154L, and E170K) that confer significantly enhanced carbapenemase activity. Compared to NDM-5, NDM-17 had only one amino acid substitution (E170K) and slightly increased isolate resistance to carbapenem, as indicated by increased MIC values. The gene encoding NDM-17 (blaNDM-17) was located on an IncX3 plasmid, which was readily transferrable to recipientE. colistrain J53 by conjugation, suggesting the possibility of the rapid dissemination ofblaNDM-17Enzyme kinetics showed that NDM-17 could hydrolyze all β-lactams tested, except for aztreonam, and had a significantly higher affinity for all β-lactams tested than did NDM-5. The emergence of this novel NDM variant could pose a threat to public health because of its transferability and enhanced carbapenemase activity.
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Microbiology and Infectious Disease, Cardiff Institute of Infection & Immunity, Heath Park Hospital, Cardiff, United Kingdom.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Walsh
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zhangqi
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Rongmin
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Yin
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Yao
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Jiyun
authors.identifier: 0000-0003-4877-8199
authors.initials: J
authors.lastname: Li
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China sjz@cau.edu.cn.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D000073182:Carbapenem-Resistant Enterobacteriaceae / Q000187:drug effects / Q000235:genetics*; D002645:Chickens; D002681:China; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D029968:Escherichia coli Proteins / Q000235:genetics*; D022761:Gene Transfer, Horizontal / Q000235:genetics; D008826:Microbial Sensitivity Tests; D010957:Plasmids / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D047090:beta-Lactams; D001618:beta-Lactamases; C000625811:beta-lactamase NDM-17, E coli; C063912:carbapenemase
keywords: IncX3; NDM-17; ST48; carbapenemase