AmpC beta-lactamase in an Escherichia coli clinical isolate confers resistance to expanded-spectrum cephalosporins

Abstract

Cloning, sequencing, and biochemical analysis identified a novel AmpC-type beta-lactamase conferring resistance to extended-spectrum cephalosporins in an Escherichia coli clinical isolate. This enzyme, exhibiting 14 amino acid substitutions compared to a reference AmpC cephalosporinase of E. coli, hydrolyzed ceftazidime and cefepime significantly.

FIG. 1.

Comparison of amino acid sequences of AmpC KL and AmpC S4 with those of other AmpC β-lactamases. The sources of the enzymes are as follows: AmpC K12 is from E. coli K12 (5), AmpC CHE is from E. cloacae CHE (2), and AmpC HD is from S. marcescens (15). β-Lactamases AmpC KL, AmpC CHE, and AmpC HD confer resistance to cefepime. The arrow indicates cleavage of the peptide leader site for AmpC K12. Amino acid residues of AmpC CHE and AmpC HD that were deleted compared to those of the wild-type cephalosporinase appear in black dashes on a grey background (2, 15). Dashes have been introduced to optimize the alignment, and dots indicate amino acid residues identical to those of AmpC KL. Conserved residues of class C β-lactamases are underlined.