Substrate selectivity and a novel role in inhibitor discrimination by residue 237 in the KPC-2 beta-lactamase.

ABSTRACT: Beta-lactamase-mediated antibiotic resistance continues to challenge the contemporary treatment of serious bacterial infections. The KPC-2 beta-lactamase, a rapidly emerging gram-negative resistance determinant, hydrolyzes all commercially available beta-lactams, including carbapenems and beta-lactamase inhibitors; the amino acid sequence requirements responsible for this versatility are not yet known. To explore the bases of beta-lactamase activity, we conducted site saturation mutagenesis at Ambler position 237. Only the T237S variant of the KPC-2 beta-lactamase expressed in Escherichia coli DH10B maintained MICs equivalent to those of the wild type (WT) against all of the beta-lactams tested, including carbapenems. In contrast, the T237A variant produced in E. coli DH10B exhibited eleva

SUBMITTER: Papp-Wallace KM 

PROVIDER: S-EPMC2897288 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature