OXA-163, an OXA-48-related class D β-lactamase with extended activity toward expanded-spectrum cephalosporins

Abstract

Two bla(OXA-48)-like-positive isolates (Klebsiella pneumoniae and Enterobacter cloacae) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in Enterobacteriaceae. In both cases, sequencing identified β-lactamase OXA-163, differing from OXA-48 by a single amino substitution and a 4-amino-acid deletion. OXA-163 hydrolyzed penicillins, ceftazidime, and cefotaxime, whereas OXA-48 did not. However, OXA-163 had a much lower ability to hydrolyze carbapenems than OXA-48, therefore barely being considered a carbapenemase. In both isolates, the bla(OXA-163) gene was located on plasmids that differed in structure and size. However, a detailed genetic analysis revealed a similar genetic context in those isolates, with the bla(OXA-163) gene being bracketed by novel transposase genes, making this genetic environment different from that reported for the bla(OXA-48) gene. This study identified the first class D β-lactamase compromising both extended-spectrum cephalosporin and carbapenem activities.

Fig. 1.

Amino acid alignment of the OXA-163 and OXA-48 amino acid sequences. Dashes indicate amino acids identical to those in the OXA-48 sequence. Absence of dashes indicates absence of residues at those positions. Amino acid motifs which are well conserved among class D β-lactamases are shaded in gray. Numbering is according to DBL (8).

Fig. 2.

(A) Schematic representation of genetic environment of the bla_OXA-163 gene in isolates Enc2185 and Kp6299; (B) schematic representation of the genetic environment of the bla_OXA-48 gene. The coding regions are shown as horizontal boxes, with an arrow indicating the orientation of transcription. Restriction sites are indicated. Inverted repeats are indicated as vertical boxes. Vertical dashed lines indicate identity between recombinant plasmids p2185 and p6299. Black triangles stand for terminal site duplication after Tn1999 insertion.