Class D β-Lactamases: Are They All Carbapenemases?

Abstract

ABSTRACTCarbapenem-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 inAcinetobacterspp., notably inAcinetobacter baumannii. The OXA-2 and OXA-10 enzymes predominantly occur inPseudomonas aeruginosaand are currently classified as narrow-spectrum class D β-lactamases. Here we demonstrate that when OXA-2 and OXA-10 are expressed inEscherichia colistrain JM83, they produce a narrow-spectrum antibiotic resistance pattern. When the enzymes are expressed inA. baumanniiATCC 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.