title: First report of a novel extended-spectrum beta-lactamase KOXY-2 producing Klebsiella oxytoca that hydrolyses cefotaxime and ceftazidime.
abstract: Klebsiella oxytoca strains MU946294N and MB193997E were isolated from patients in Scotland. Strain MU946294N was resistant to pencillins, monbactams and cephalosporins. Isolate MB193997E displayed a β-lactam resistance phenotype consistent with chromosomal β-lactamase overproduction. No bla(TEM), bla(SHV) or bla(CTX-M) genes could be amplified in either strain; however, amplification by PCR was found with primers for the bla(OXY-2) gene. This β-lactamase gene in MU946294N differed by one mutation from the all other bla(OXY) genes previously reported, with an amino acid substitution Alanine237 Threonine enhancing the binding of cefotaxime. Strain MB193997E showed mutations at positions 255 and 283, neither of which affect function. Based on rpoB and gyrA characterization, both strains were assigned to the KoII phylogenic group but they were completely dissimilar from each other by PFGE. This study is the first to report the substitution of Alanine to Threonine at position 237 in a OXY- 2 β-lactamase and this enhances resistance to cefotaxime.
authors: Centre for Infectious Diseases, University of Edinburgh, 49 Little France Crescent, Edinburgh, UK.
authors: A
authors: A
authors: Younes
authors: A
authors: A
authors: Hamouda
authors: S G B
authors: SG
authors: Amyes
mesh_terms: D000409:Alanine / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D002439:Cefotaxime / Q000737:chemistry* / Q000493:pharmacokinetics; D002442:Ceftazidime / Q000737:chemistry* / Q000493:pharmacokinetics; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D041121:Klebsiella oxytoca / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D009154:Mutation; D012606:Scotland; D013912:Threonine / Q000235:genetics; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D013912:Threonine; D002442:Ceftazidime; D001618:beta-Lactamases; D027081:DNA Gyrase; D002439:Cefotaxime; D000409:Alanine