Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4

Daniel J. Wolter, Philip M. Kurpiel, Neil Woodford, Marie France I Palepou, Richard V. Goering, Nancy D. Hanson

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)557-562
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume53
Issue number2
DOIs
StatePublished - Feb 2009

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Klebsiella pneumoniae
Klebsiella pneumoniae carbapenemase-2
carbapenemase
Carbapenems
Hydrolysis
Enzymes
Puerto Rico
Clavulanic Acid
Ceftazidime
Imipenem
Amino Acid Substitution
Pseudomonas aeruginosa

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Phenotypic and enzymatic comparative analysis of the novel KPC variant KPC-5 and its evolutionary variants, KPC-2 and KPC-4. / Wolter, Daniel J.; Kurpiel, Philip M.; Woodford, Neil; Palepou, Marie France I; Goering, Richard V.; Hanson, Nancy D.

In: Antimicrobial Agents and Chemotherapy, Vol. 53, No. 2, 02.2009, p. 557-562.

Research output: Contribution to journalArticle

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