title: Promoter deletions of Klebsiella pneumoniae carbapenemase (KPC)-encoding genes (blaKPC -2) and efflux pump (AcrAB) on β-lactam susceptibility in KPC-producing Enterobacteriaceae.
abstract: Klebsiella pneumoniae carbapenemase (KPC)-encoding genes containing promoter-deletions (bla(KPC-2a), bla(KPC-2b), and bla(KPC-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 bla(KPC-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 bla(KPC-2a), bla(KPC-2b), and bla(KPC-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 bla(KPC-2a), bla(KPC-2b), and bla(KPC-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 bla(KPC-2) gene and AcrAB may be associated with the variability in β-lactam MICs in KPC-producing Enterobacteriaceae.
authors.affiliation: Department of Biology, Long Island University, Brooklyn, NY, USA.
authors.forename: Gomattie D
authors.initials: GD
authors.lastname: Seecoomar
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Marmol
authors.forename: Dong H
authors.initials: DH
authors.lastname: Kwon
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005838:Genotype; D007711:Klebsiella pneumoniae / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D011401:Promoter Regions, Genetic / Q000235:genetics; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D001618:beta-Lactamases; C063912:carbapenemase
keywords: Enterobacteriaceae; carbapenemase; efflux pump
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