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Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India

 Dongeun Yong  ;  Mark A. Toleman  ;  Christian G. Giske  ;  Hyun S. Cho  ;  Kristina Sundman  ;  Kyungwon Lee  ;  Timothy R. Walsh 
Journal Title
Issue Date
Amino Acid Sequence ; Anti-Bacterial Agents/metabolism ; Anti-Bacterial Agents/pharmacology ; Carboxylic Ester Hydrolases/chemistry* ; Carboxylic Ester Hydrolases/classification ; Carboxylic Ester Hydrolases/genetics* ; Cefotaxime/metabolism ; Cefotaxime/pharmacology ; Cefuroxime/metabolism ; Cefuroxime/pharmacology ; Cephalosporins/metabolism ; Cephalosporins/pharmacology ; Cephalothin/metabolism ; Cephalothin/pharmacology ; Drug Resistance, Multiple, Bacterial/genetics ; Drug Resistance, Multiple, Bacterial/physiology ; Electrophoresis, Gel, Pulsed-Field ; Humans ; India ; Kinetics ; Klebsiella Infections/microbiology* ; Klebsiella pneumoniae/drug effects ; Klebsiella pneumoniae/enzymology* ; Klebsiella pneumoniae/genetics* ; Microbial Sensitivity Tests ; Molecular Sequence Data ; Penicillins/metabolism ; Penicillins/pharmacology ; Sequence Analysis, DNA ; Sequence Homology, Amino Acid ; beta-Lactamases/chemistry* ; beta-Lactamases/classification ; beta-Lactamases/genetics*
A Swedish patient of Indian origin traveled to New Delhi, India, and acquired a urinary tract infection caused by a carbapenem-resistant Klebsiella pneumoniae strain that typed to the sequence type 14 complex. The isolate, Klebsiella pneumoniae 05-506, was shown to possess a metallo-beta-lactamase (MBL) but was negative for previously known MBL genes. Gene libraries and amplification of class 1 integrons revealed three resistance-conferring regions; the first contained bla(CMY-4) flanked by ISEcP1 and blc. The second region of 4.8 kb contained a complex class 1 integron with the gene cassettes arr-2, a new erythromycin esterase gene; ereC; aadA1; and cmlA7. An intact ISCR1 element was shown to be downstream from the qac/sul genes. The third region consisted of a new MBL gene, designated bla(NDM-1), flanked on one side by K. pneumoniae DNA and a truncated IS26 element on its other side. The last two regions lie adjacent to one another, and all three regions are found on a 180-kb region that is easily transferable to recipient strains and that confers resistance to all antibiotics except fluoroquinolones and colistin. NDM-1 shares very little identity with other MBLs, with the most similar MBLs being VIM-1/VIM-2, with which it has only 32.4% identity. As well as possessing unique residues near the active site, NDM-1 also has an additional insert between positions 162 and 166 not present in other MBLs. NDM-1 has a molecular mass of 28 kDa, is monomeric, and can hydrolyze all beta-lactams except aztreonam. Compared to VIM-2, NDM-1 displays tighter binding to most cephalosporins, in particular, cefuroxime, cefotaxime, and cephalothin (cefalotin), and also to the penicillins. NDM-1 does not bind to the carbapenems as tightly as IMP-1 or VIM-2 and turns over the carbapenems at a rate similar to that of VIM-2. In addition to K. pneumoniae 05-506, bla(NDM-1) was found on a 140-kb plasmid in an Escherichia coli strain isolated from the patient's feces, inferring the possibility of in vivo conjugation. The broad resistance carried on these plasmids is a further worrying development for India, which already has high levels of antibiotic resistance
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1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Yong, Dong Eun(용동은) ORCID logo https://orcid.org/0000-0002-1225-8477
Lee, Kyungwon(이경원) ORCID logo https://orcid.org/0000-0003-3788-2134
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