title: Inhibitor-resistant OXY-2-derived beta-lactamase produced by Klebsiella oxytoca.
abstract: Klebsiella oxytoca strains are generally moderately resistant to amoxicillin and ticarcillin due to the activities of the chromosomally encoded OXY-1 and OXY-2 class A beta-lactamase families. These enzymes have the ability to hydrolyze not only penicillins but also cephalosporins, including cefuroxime, ceftriaxone, and aztreonam, and are inhibited by clavulanic acid. A Klebsiella oxytoca strain was isolated from a culture of blood from a patient who had been treated with amoxicillin-clavulanate (3 g/day) for 10 days 1 month earlier. This strain harbored an unusual phenotype characterized by resistance to amoxicillin-clavulanate. It produced an OXY-2-type beta-lactamase (pI 6.3), as confirmed by PCR amplification with primers specific for the OXY-2-encoding gene. Gene sequencing revealed a point mutation (A-->G) corresponding to the amino acid substitution Ser-->Gly at position 130. This mutant enzyme was poorly inhibited by inhibitors, and its kinetic constants compared to those of the parent enzyme were characterized by an increased Km value for ticarcillin, with a drastically reduced activity against cephalosporins, as is observed with inhibitor-resistant TEM enzymes. The substitution Ser-->Gly-130 was previously described in the inhibitor-resistant beta-lactamase SHV-10 derived from an SHV-5 variant, but this is the first report of such a mutant in OXY enzymes from K. oxytoca.
authors.affiliation: Laboratoire de Bactériologie, Faculté de Médecine, 63001 Clermont-Ferrand Cedex, France. Danielle. SIROT@u-clermont1.fr
authors.forename: D
authors.initials: D
authors.lastname: Sirot
authors.forename: R
authors.initials: R
authors.lastname: Labia
authors.forename: P
authors.initials: P
authors.lastname: Pouedras
authors.forename: C
authors.initials: C
authors.lastname: Chanal-Claris
authors.forename: C
authors.initials: C
authors.lastname: Cerceau
authors.forename: J
authors.initials: J
authors.lastname: Sirot
mesh_terms: D004352:Drug Resistance, Microbial; D007525:Isoelectric Focusing; D007709:Klebsiella / Q000187:drug effects* / Q000201:enzymology; D010641:Phenotype; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases