Molecular characterization of TEM-59 (IRT-17), a novel inhibitor-resistant TEM-derived beta-lactamase in a clinical isolate of Klebsiella oxytoca

Antimicrob Agents Chemother. 1999 Jul;43(7):1657-61. doi: 10.1128/AAC.43.7.1657.

Abstract

A clinical isolate of Klebsiella oxytoca (Kox 443) was found to have a low-level resistance to broad-spectrum penicillins (MICs of amoxicillin and ticarcillin, 256 and 32 microg/ml, respectively), without substantial potentiation by 2 microg of clavulanic acid per ml (amoxicillin- and ticarcillin-clavulanate, 128 and 8 microg/ml, respectively), while being fully susceptible to cephalosporins and other beta-lactam antibiotics. These resistances were carried by a ca. 50-kb conjugative plasmid that encodes a single beta-lactamase with a pI of 5.6. Compared to TEM-2, this enzyme exhibited a 3- to 30-fold higher Km and a decreased maximal hydrolysis rate for beta-lactams; higher concentrations of suicide inactivators (5- to 500-fold higher concentrations giving a 50% reduction in hydrolysis) were required for inhibition. Nucleotide sequence analysis revealed identity between the blaTEM gene of Kox 443 and the blaTEM-2 gene, except for a single A-to-G change at position 590, leading to the amino acid change from Ser-130 Gly. This mutation has not been reported previously in the TEM type beta-lactamases produced by clinical strains, and the novel enzyme was called TEM-59 (alternative name IRT-17). This is the first description of an inhibitor-resistant TEM-derived enzyme in the species K. oxytoca.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Drug Resistance, Microbial
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Humans
  • Klebsiella / enzymology*
  • Mutation
  • Polymerase Chain Reaction
  • beta-Lactamase Inhibitors
  • beta-Lactamases / genetics*

Substances

  • Enzyme Inhibitors
  • beta-Lactamase Inhibitors
  • beta-Lactamases

Associated data

  • GENBANK/AF062386