Characterization of a New Metallo-β-Lactamase Gene, <i>bla</i> <sub>NDM-1</sub> , and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in <i>Klebsiella pneumoniae</i> Sequence Type 14 from India

Antimicrobial Agents and Chemotherapy - Tập 53 Số 12 - Trang 5046-5054 - 2009
Dongeun Yong1,2, Antoine Andremont1, Christian G. Giske3, Hyun S. Cho4, Kristina Sundman5, Kyungwon Lee2, Timothy R. Walsh1
1Department of Medical Microbiology, Cardiff University, Cardiff, United Kingdom
2Yonsei University College of Medicine, Research Institute of Antimicrobial Resistance, Seoul, Republic of Korea
3Clinical Microbiology, MTC—Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
4Yonsei University College of Life Science and Biotechnology, Seoul, Republic of Korea
5Department of Clinical Microbiology, Örebro University Hospital, Örebro, Sweden

Tóm tắt

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-β-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 IS EcP1 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 IS CR1 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 IS 26 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 β-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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Antimicrobial Agents and Chemotherapy

Tập 53 Số 12

5046-5054

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