Promoter deletions of Klebsiella pneumoniae carbapenemase (KPC)-encoding genes (blaKPC-2) and efflux pump (AcrAB) on β-lactam susceptibility in KPC-producing Enterobacteriaceae

Authors

  • Gomattie D. Seecoomar,

    1. Department of Biology, Long Island University, Brooklyn, NY, USA
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  • Brenda C. Marmol,

    1. Department of Biology, Long Island University, Brooklyn, NY, USA
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  • Dong H. Kwon

    Corresponding author
    1. Department of Biology, Long Island University, Brooklyn, NY, USA
    2. Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA
    • Correspondence: Dong H. Kwon, Biology Department, Long Island University, One University Plaza, Brooklyn, NY 11201, USA. Tel.: +1 718 7804098; fax: +1 718 4881465; e-mail: dong.kwon@liu.edu

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Abstract

Klebsiella pneumoniae carbapenemase (KPC)-encoding genes containing promoter-deletions (blaKPC-2a, blaKPC-2b, and blaKPC-2c) have disseminated in Enterobacteriaceae. The minimal inhibitory concentrations (MICs) to β-lactams in clinical KPC-producing Enterobacteriaceae range from susceptible to high-level resistant, resulting in diagnostic problems. To better understand the variability in β-lactam MICs among KPC-producing Enterobacteriaceae, three isoforms of blaKPC-2 gene were used to transform Escherichia coli W4573 and its deletion mutant of an efflux pump (AcrAB) to examine the effects on β-lactam susceptibility. MICs to β-lactams in E. coli W4573 and its acrAB mutant strain increased 1- to 500-fold (MIC from 0.125 to 64 μg mL−1 of aztreonam) in the blaKPC-2a, blaKPC-2b, and blaKPC-2c transformants compared with the cloning vector alone. However, transformants of the acrAB mutant strain remained susceptible to all β-lactams tested except for aztreonam and carbenicillin. Levels of the three promoters’ length and carbapenemase activities in the transformants harboring the blaKPC-2a, blaKPC-2b, and blaKPC-2c were correlated to the levels of β-lactam MICs in both E. coli W4573 and its mutant of an efflux pump (AcrAB). Overall, these results suggest that promoter-deletions of blaKPC-2 gene and AcrAB may be associated with the variability in β-lactam MICs in KPC-producing Enterobacteriaceae.

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