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KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States - Volume 21, Number 6—June 2015 - Emerging Infectious Disease journal - CDC

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KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States - Volume 21, Number 6—June 2015 - Emerging Infectious Disease journal - CDC

Volume 21, Number 6—June 2015


KPC and NDM-1 Genes in Related Enterobacteriaceae Strains and Plasmids from Pakistan and the United States

Mitchell W. Pesesky1, Tahir Hussain1, Meghan Wallace, Bin Wang, Saadia Andleeb, Carey-Ann D. Burnham, and Gautam DantasComments to Author 
Author affiliations: Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA (M.W. Pesesky, T. Hussain. M. Wallace, B. Wang, C.D. Burnham, G. Dantas)National University of Sciences and Technology, Islamabad, Pakistan (T. Hussain, S. Andleeb)


To characterize the genomic context of New Delhi metallo-β-lactamase-1 (NDM-1) and Klebsiella pneumoniae carbapenemase (KPC), we sequenced 78 Enterobacteriaceae isolates from Pakistan and the United States encoding KPC, NDM-1, or no carbapenemase. High similarities of the results indicate rapid spread of carbapenem resistance between strains, including globally disseminated pathogens.
Pathogenic Enterobacteriaceae, including Escherichia coli and Klebsiella pneumoniae, are major causes of multidrug-resistant (MDR) infections in hospitals worldwide. These pathogens have recently been shown to have acquired resistance to carbapenems, and the US Centers for Disease Control and Prevention identified carbapenem-resistant Enterobacteriaceae as of the 3 most urgent MDR threats (1). Among theEnterobacteriaceae, β-lactam resistance, including carbapenem resistance, is primarily caused by enzymatic degradation by β-lactamases. Two carbapenemase subclasses are especially problematic: Klebsiella pneumoniaecarbapenemase (KPC) and New Delhi metallo-β-lactamase-1 (NDM-1). KPC, identified in 2001 (2), has become endemic to several noncontiguous areas of the world, including the United States, Israel, Greece, South America, and China (3). NDM-1 was first described in 2008, although retrospective studies identified NDM-1 from 2006 (4) and is abundant in New Delhi water samples (5). Most patients from whom NDM-1 is isolated have an epidemiologic link to the Indian subcontinent, but NDM-1 has also recently become endemic to the Balkans and Middle East (6).
The spread of antibiotic resistance genes such as NDM-1 and KPC is facilitated by horizontal gene transfer (HGT) between bacteria (7). Among globally disseminated pathogens, HGT facilitates combination of the most effective antibiotic resistance genes from diverse geographies into multidrug resistance plasmids that spread between strains. Recombination and transposition have created populations of these plasmids that have related architectures but vary in their composition of antibiotic drug resistance cassettes (8). This effect has enabled both KPC and NDM-1 to rapidly expand within theEnterobacteriaceae and other proteobacterial pathogens, such as Acinetobacter baumanii (9,10). Antibiotic resistance genes can also spread through clonal expansion in successful pathogenic strains, for example, KPC in K. pneumoniae sequence type (ST) 258 (11), and the extended-spectrum β-lactamase CTX-M-15 in E. coli ST131 (12). Both HGT and clonal expansion have enabled KPC and NDM-1 to rapidly spread to distant locations after their emergence (6,8).
The similarities in the spread and resistance spectra of KPC and NDM-1 (both provide resistance to nearly all β-lactam antimicrobial drugs) leads to the hypothesis that similar mobile elements will make both genes available to similar pathogen populations. We tested this hypothesis by examining clinicalEnterobacteriaceae isolates from Pakistan and the United States encoding NDM-1, KPC, or no carbapenemase.
Dr. Pesesky received his PhD from Washington University in St. Louis, Missouri, USA, in 2015 and is currently a postdoctoral fellow at the University of Washington, Seattle, Washington, USA. His research focuses on molecular and genomic investigations of high interest functions in bacteria.


We thank members of the Dantas lab for thoughtful discussions of the research described herein.
Research reported in this publication was supported in part by the National Institutes of Health Director’s New Innovator Award (http://commonfund.nih.gov/newinnovator/), the National Institute of Diabetes and Digestive and Kidney Diseases (http://www.niddk.nih.gov/), and the National Institute of General Medical Sciences (NIGMS: http://www.nigms.nih.gov/), of the National Institutes of Health under award numbers DP2DK098089 and R01GM099538 to G.D. M.W.P. is supported by the NIGMS Cell and Molecular Biology Training Grant (GM:007067). T.H. is supported by the Higher Education Commission of Pakistan’s International Research Support Initiative Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. All genome and plasmid sequences were deposited into the National Center for Biotechnology Information database (http://www.ncbi.nlm.nih.gov) (BioProject ID PRJNA261540).


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Technical Appendix

Suggested citation for this article: Pesesky MW, Hussain T, Wallace M, Wang B, Andleeb S, Burnham CD, et al. KPC and NDM-1 genes in relatedEnterobacteriaceae strains and plasmids from Pakistan and the United States. Emerg Infect Dis. 2015 Jun [date cited].http://dx.doi.org/10.3201/eid2106.141504
DOI: 10.3201/eid2106.141504
1These first authors contributed equally to this article.

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