Resistance Determinants and Mobile Genetic Elements of an NDM-1-Encoding Klebsiella pneumoniae Strain

Hudson, Corey M.; Bent, Zachary W.; Meagher, Robert J.; Williams, Kelly P.

doi:10.1371/journal.pone.0099209

Title: Resistance Determinants and Mobile Genetic Elements of an NDM-1-Encoding Klebsiella pneumoniae Strain

Journal Article · Fri Jun 06 00:00:00 EDT 2014 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0099209· OSTI ID:1627702

Hudson, Corey M. ^[1]; Bent, Zachary W. ^[1]; Meagher, Robert J. ^[2]; Williams, Kelly P. ^[1]

Sandia National Lab. (SNL-CA), Livermore, CA (United States). Dept. of Systems Biology
Sandia National Lab. (SNL-CA), Livermore, CA (United States). Dept. of Biotechnology and Bioengineering

Multidrug-resistant Enterobacteriaceae are emerging as a serious infectious disease challenge. These strains can accumulate many antibiotic resistance genes though horizontal transfer of genetic elements, those for b-lactamases being of particular concern. Some b-lactamases are active on a broad spectrum of b-lactams including the last-resort carbapenems. The gene for the broad-spectrum and carbapenem-active metallo-b-lactamase NDM-1 is rapidly spreading. We present the complete genome of Klebsiella pneumoniae ATCC BAA-2146, the first U.S. isolate found to encode NDM-1, and describe its repertoire of antibiotic-resistance genes and mutations, including genes for eight b-lactamases and 15 additional antibiotic-resistance enzymes. To elucidate the evolution of this rich repertoire, the mobile elements of the genome were characterized, including four plasmids with varying degrees of conservation and mosaicism and eleven chromosomal genomic islands. One island was identified by a novel phylogenomic approach, that further indicated the cps-lps polysaccharide synthesis locus, where operon translocation and fusion was noted. Unique plasmid segments and mosaic junctions were identified. Plasmid-borne blaCTX-M-15 was transposed recently to the chromosome by ISEcp1. None of the eleven full copies of IS26, the most frequent IS element in the genome, had the expected 8-bp direct repeat of the integration target sequence, suggesting that each copy underwent homologous recombination subsequent to its last transposition event. Comparative analysis likewise indicates IS26 as a frequent recombinational junction between plasmid ancestors, and also indicates a resolvase site. In one novel use of high-throughput sequencing, homologously recombinant subpopulations of the bacterial culture were detected. In a second novel use, circular transposition intermediates were detected for the novel insertion sequence ISKpn21 of the ISNCY family, suggesting that it uses the two-step transposition mechanism of IS3. Robust genome-based phylogeny showed that a unified Klebsiella cluster contains Enterobacter aerogenes and Raoultella, suggesting the latter genus should be abandoned.

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Research Organization:: Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC04-94AL85000

OSTI ID:: 1627702

Journal Information:: PLoS ONE, Vol. 9, Issue 6; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

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