Molecular characterization of TEM-59 (IRT-17), a novel inhibitor-resistant TEM-derived beta-lactamase in a clinical isolate of Klebsiella oxytoca.
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.
Bermudes
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Laboratoire de Microbiologie, UFR des Sciences Pharmaceutiques, Université de Bordeaux 2, 33076 Bordeaux Cedex, France.
Jude
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Chaibi
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Arpin
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Bebear
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Labia
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Quentin
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C
D000368:Aged; D000369:Aged, 80 and over; D004352:Drug Resistance, Microbial; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007709:Klebsiella / Q000201:enzymology*; D009154:Mutation; D016133:Polymerase Chain Reaction; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics*
D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases