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

Antimicrob Agents Chemother. 2009 Dec;53(12):5046-54. doi: 10.1128/AAC.00774-09. Epub 2009 Sep 21.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Anti-Bacterial Agents
  • Cephalosporins
  • Penicillins
  • Carboxylic Ester Hydrolases
  • erythromycin esterase
  • beta-Lactamases
  • Cefotaxime
  • Cefuroxime
  • Cephalothin

Associated data

  • GENBANK/FN396876