期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 70, 期 4, 页码 1059-1063出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dku524
关键词
carbapenemases; class D beta-lactamases; enzymatic activity
资金
- INSERM [UMR914]
- University of Fribourg (Switzerland)
- ANR [ANR-10-LABX-33]
Objectives: Carbapenem-hydrolysing class D beta-lactamases of the OXA-48 type are increasingly reported from Enterobacteriaceae. beta-Lactamase OXA-48 hydrolyses penicillins very efficiently, but carbapenems only weakly and spares broad-spectrum cephalosporins. Recently, diverse OXA-48-like beta-lactamases have been identified worldwide (OXA-162, OXA-181, OXA-163, OXA-204 and OXA-232). They differ by few amino acid substitutions or by amino acid deletions. Methods: bla(OXA-48), bla(OXA-162), bla(OXA-163), bla(OXA-181), bla(OXA-204) and bla(OXA-232) were cloned into the same expression vector and expressed in the same Escherichia coli background. Kinetic studies were performed with enzymes purified by ion-exchange chromatography. Determination of hydrolytic activities was performed by UV spectrophotometry. MICs were determined for all recombinant strains, using as background either the WT E. coli TOP10 strain or a porin-deficient E. coli strain. Results: Kinetic studies showed that OXA-162 and OXA-204 shared the same hydrolytic properties as OXA-48. On the other hand, OXA-181 possessed a higher ability to hydrolyse carbapenems, while OXA-232 hydrolysed those substrates less efficiently. In contrast to the other OXA-48-like beta-lactamases, OXA-163 hydrolysed broad-spectrum cephalosporins very efficiently, but did not possess significant carbapenemase activity. Although several of these OXA-48-like enzymes possess low activity against carbapenems, MICs of carbapenems were significantly elevated when determined for strains possessing permeability defects. Conclusions: A detailed comparative analysis of the kinetic properties of the OXA-48-like beta-lactamases is provided here. It clarifies the respective features of each OXA-48-like variant and their respective impacts in terms of carbapenem resistance.
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