A novel ceftazidime-hydrolysing extended-spectrum β-lactamase, CTX-M-54, with a single amino acid substitution at position 167 in the omega loop

Kwon Bae, Byung Ho Lee, Hyun Yong Hwang, Seok Hoon Jeong, Seong Geun Hong, Chulhun L. Chang, Hyo Sun Kwak, Hyoung Jin Kim, Hasik Youn

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39 Citations (Scopus)

Abstract

Objectives: To characterize a novel ceftazidime-hydrolysing CTX-M mutant, designated CTX-M-54, produced by Klebsiella pneumoniae clinical isolate BDK0419 and to investigate its genetic environment. Methods: Antimicrobial susceptibilities were determined by disc diffusion and agar dilution methods, and the double-disc synergy test was carried out. Detection of genes encoding class A β-lactamases was performed by PCR amplification, and the genetic organization of the blaCTX-M-54 gene was investigated by PCR and sequencing of the regions surrounding this gene. Kinetic parameters were determined from purified CTX-M-54. Results: The strain BDK0419 contained a transferable plasmid with a molecular size of ∼21 kbp that carries both blaSHV-2a and blaCTX-M-54 β-lactamase genes, along with two other plasmids. The blaCTX-M-54 gene was flanked upstream by an IS Ecp1 insertion sequence and downstream by an IS 903-like element. CTX-M-54 had a P167Q substitution within the omega loop region of class A β-lactamases compared with the sequence of CTX-M-3. The MIC of ceftazidime for K. pneumoniae BDK0419 was 16-fold higher than that of cefotaxime; however, the kinetic parameter of CTX-M-54 against ceftazidime revealed a low catalytic efficiency. Conclusions: This work shows once again that novel CTX-M enzymes with an expanded activity towards ceftazidime through a single amino acid substitution can be identified from clinical isolates. Thus, detection of CTX-M enzymes can no longer be based solely on the resistance phenotypes of clinical isolates towards ceftazidime and cefotaxime.

Original languageEnglish
Pages (from-to)315-319
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
Volume58
Issue number2
DOIs
Publication statusPublished - 2006 Aug 1

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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