title: 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.
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.
authors.affiliation: Yonsei University College of Medicine, Research Institute of Antimicrobial Resistance, Seoul, Republic of Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Yong
authors.forename: Mark A
authors.initials: MA
authors.lastname: Toleman
authors.forename: Christian G
authors.initials: CG
authors.lastname: Giske
authors.forename: Hyun S
authors.initials: HS
authors.lastname: Cho
authors.forename: Kristina
authors.initials: K
authors.lastname: Sundman
authors.forename: Kyungwon
authors.initials: K
authors.lastname: Lee
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Walsh
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D002439:Cefotaxime / Q000378:metabolism / Q000494:pharmacology; D002444:Cefuroxime / Q000378:metabolism / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism / Q000494:pharmacology; D002512:Cephalothin / Q000378:metabolism / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics / Q000502:physiology; D016521:Electrophoresis, Gel, Pulsed-Field; D006801:Humans; D007194:India; D007700:Kinetics; D007710:Klebsiella Infections / Q000382:microbiology*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010406:Penicillins / Q000378:metabolism / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D001618:beta-Lactamases / Q000737:chemistry* / Q000145:classification / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D010406:Penicillins; D002265:Carboxylic Ester Hydrolases; C046388:erythromycin esterase; D001618:beta-Lactamases; D002439:Cefotaxime; D002444:Cefuroxime; D002512:Cephalothin