Class D β-lactamases: are they all carbapenemases?
Carbapenem-hydrolyzing class D β-lactamases (CHDLs) are enzymes of the utmost clinical importance due to their ability to produce resistance to carbapenems, the antibiotics of last resort for the treatment of various life-threatening infections. The vast majority of these enzymes have been identified in Acinetobacter spp., notably in Acinetobacter baumannii. The OXA-2 and OXA-10 enzymes predominantly occur in Pseudomonas aeruginosa and are currently classified as narrow-spectrum class D β-lactamases. Here we demonstrate that when OXA-2 and OXA-10 are expressed in Escherichia coli strain JM83, they produce a narrow-spectrum antibiotic resistance pattern. When the enzymes are expressed in A. baumannii ATCC 17978, however, they behave as extended-spectrum β-lactamases and confer resistance to carbapenem antibiotics. Kinetic studies of OXA-2 and OXA-10 with four carbapenems have demonstrated that their catalytic efficiencies with these antibiotics are in the same range as those of some recognized class D carbapenemases. These results are in disagreement with the classification of the OXA-2 and OXA-10 enzymes as narrow-spectrum β-lactamases, and they suggest that other class D enzymes that are currently regarded as noncarbapenemases may in fact be CHDLs.
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana, USA.
Nuno T
NT
Antunes
Toni L
TL
Lamoureaux
Marta
M
Toth
Nichole K
NK
Stewart
Hilary
H
Frase
Sergei B
SB
Vakulenko
D040981:Acinetobacter baumannii / Q000187:drug effects / Q000201:enzymology; D001426:Bacterial Proteins / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism*
D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase