Characterization of a New Metallo-β-Lactamase Gene, blaNDM-1, and a Novel Erythromycin Esterase Gene Carried on a Unique Genetic Structure in Klebsiella pneumoniae Sequence Type 14 from India
Dongeun Yong,Mark Toleman,Christian G. Giske,Hyun Sun Cho,Kristina Sundman,Kyungwon Lee,Timothy R. Walsh +6 more
TLDR
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, showing broad resistance carried on these plasmids.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 blaCMY-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 blaNDM-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 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, blaNDM-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.read more
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Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study
Karthikeyan Kumarasamy,Mark Toleman,Timothy R. Walsh,Jay Bagaria,Fafhana Butt,Ravikumar Balakrishnan,Uma Chaudhary,Michel Doumith,Christian G. Giske,Seema Irfan,Padma Krishnan,Anil Kumar,Sunil Maharjan,Shazad Mushtaq,Tabassum Noorie,David L. Paterson,A. Pearson,Claire Perry,Rachel Pike,Bhargavi Rao,Ujjwayini Ray,Jayanta B. Sarma,Madhu Sharma,Elizabeth Sheridan,M A Thirunarayan,Jane F. Turton,Supriya Upadhyay,Marina Warner,William Welfare,David M. Livermore,Neil Woodford +30 more
TL;DR: The prevalence of NDM-1, in multidrug-resistant Enterobacteriaceae in India, Pakistan, and the UK is investigated, and co-ordinated international surveillance is needed.
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Global spread of Carbapenemase-producing Enterobacteriaceae.
TL;DR: These resistance traits have been identified among nosocomial and community-acquired infections and are being investigated for use in drug discovery and development.
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Antibiotics and Bacterial Resistance in the 21st Century
Richard J. Fair,Yitzhak Tor +1 more
TL;DR: In this review the factors that have been linked to the waxing of bacterial resistance are addressed and profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated.
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The Comprehensive Antibiotic Resistance Database
Andrew G. McArthur,Nicholas Waglechner,Fazmin Nizam,Austin Yan,Marisa A. Azad,Alison J. Baylay,Kirandeep Bhullar,Marc J. Canova,Gianfranco De Pascale,Linda Ejim,Lindsay Kalan,Andrew M. King,Kalinka Koteva,Mariya Morar,Michael R. Mulvey,Jonathan S O'Brien,Andrew C. Pawlowski,Laura J. V. Piddock,Peter Spanogiannopoulos,Arlene D. Sutherland,Irene Tang,Patricia L. Taylor,Maulik N. Thaker,Wenliang Wang,Marie Yan,Tennison Yu,Gerard D. Wright +26 more
TL;DR: The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences.
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Multiplex PCR for detection of acquired carbapenemase genes
TL;DR: A rapid and reliable PCR-based technique was developed for detection of genes encoding carbapenemases belonging to different classes using optimized conditions, with PCR giving distinct amplicon sizes corresponding to the different genes for each mixture.
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