An unexpected similarity between antibiotic-resistant NDM-1 and beta-lactamase II from Erythrobacter litoralis.
10.1007/s13238-011-1027-0
- Author:
Beiwen ZHENG
1
;
Shuguang TAN
;
Jia GAO
;
Huiming HAN
;
Jun LIU
;
Guangwen LU
;
Di LIU
;
Yong YI
;
Baoli ZHU
;
George F GAO
Author Information
1. CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
- Publication Type:Journal Article
- MeSH:
Amino Acid Sequence;
Anti-Bacterial Agents;
pharmacology;
Aztreonam;
pharmacology;
Cephalosporinase;
chemistry;
genetics;
metabolism;
Computational Biology;
methods;
Drug Resistance, Bacterial;
genetics;
Enzyme Stability;
drug effects;
Evolution, Molecular;
Minocycline;
analogs & derivatives;
pharmacology;
Molecular Sequence Data;
Phylogeny;
Protein Structure, Tertiary;
drug effects;
Sequence Homology, Nucleic Acid;
Sphingomonadaceae;
drug effects;
enzymology;
genetics;
Tigecycline;
Zinc;
pharmacology;
beta-Lactamases;
chemistry;
genetics;
metabolism
- From:
Protein & Cell
2011;2(3):250-258
- CountryChina
- Language:English
-
Abstract:
NDM-1 (New Delhi metallo-beta-lactamase) gene encodes a metallo-beta-lactamase (MBL) with high carbapenemase activity, which makes the host bacterial strain easily dispatch the last-resort antibiotics known as carbapenems and cause global concern. Here we present the bioinformatics data showing an unexpected similarity between NDM-1 and beta-lactamase II from Erythrobacter litoralis, a marine microbial isolate. We have further expressed these two mature proteins in E. coli cells, both of which present as a monomer with a molecular mass of 25 kDa. Antimicrobial susceptibility assay reveals that they share similar substrate specificities and are sensitive to aztreonam and tigecycline. The conformational change accompanied with the zinc binding visualized by nuclear magnetic resonance, Zn(2+)-bound NDM-1, adopts at least some stable tertiary structure in contrast to the metal-free protein. Our work implies a close evolutionary relationship between antibiotic resistance genes in environmental reservoir and in the clinic, challenging the antimicrobial resistance monitoring.
