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Antimicrobial Agents and Chemotherapy, February 2009, p. 557-562, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00734-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Phenotypic and Enzymatic Comparative Analysis of the Novel KPC Variant KPC-5 and Its Evolutionary Variants, KPC-2 and KPC-4{triangledown}

Daniel J. Wolter,1 Philip M. Kurpiel,1 Neil Woodford,2 Marie-France I. Palepou,2 Richard V. Goering,3 and Nancy D. Hanson1*

Center for Research in Anti-Infectives and Biotechnology,1 Creighton University School of Medicine, Omaha, Nebraska,3 Antibiotic Resistance Monitoring and Reference Laboratory, Centre for Infections, Health Protection Agency, London, NW9 5EQ, United Kingdom2

Received 4 June 2008/ Returned for modification 8 June 2008/ Accepted 10 November 2008

A novel Klebsiella pneumoniae carbapenemase (KPC) variant, designated blaKPC-5, was discovered in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate from Puerto Rico. Characterization of the upstream region of blaKPC-5 showed significant differences from the flanking regions of other blaKPC variants. Comparison of amino acid sequences with those of other KPC enzymes revealed that KPC-5 was an intermediate between KPC-2 and KPC-4, differing from KPC-2 by a single amino acid substitution (Pro103->Arg), while KPC-4 contained Pro103->Arg plus an additional amino acid change (Val239->Gly). Transformation studies with an Escherichia coli recipient strain showed differences in the properties of the KPC variants. KPC-4 and KPC-5 both had pIs of 7.65, in contrast with the pI of 6.7 for KPC-2. KPC-2 transformants were less susceptible to the carbapenems than KPC-4 and KPC-5 transformants. These data correlated with higher rates of imipenem hydrolysis for KPC-2 than for KPC-4 and KPC-5. However, KPC-4 and KPC-5 transformants had higher ceftazidime MICs, and the enzymes from these transformants had slightly better hydrolysis of this drug than KPC-2. KPC-4 and KPC-5 were more sensitive than KPC-2 to inhibition by clavulanic acid in both susceptibility testing and hydrolysis assays. Thus, KPC enzymes may be evolving through stepwise mutations to alter their spectra of activity.

* Corresponding author. Mailing address: Center for Research in Anti-Infectives and Biotechnology, Department of Medical Microbiology and Immunology, Creighton University School of Medicine, 2500 California Plaza, Omaha, NE 68178. Phone: (402) 280-5837. Fax: (402) 280-1875. E-mail: ndhanson{at}creighton.edu

{triangledown} Published ahead of print on 17 November 2008.

Antimicrobial Agents and Chemotherapy, February 2009, p. 557-562, Vol. 53, No. 2
0066-4804/09/$08.00+0     doi:10.1128/AAC.00734-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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