Deletion Mutations Conferring Substrate Spectrum Extension in the Class A beta-Lactamase

Abstract

We describe four new deletion mutations in a class A beta-lactamase PenA in Burkholderia thailandensis, each conferring an extended substrate spectrum. Single-amino-acid deletions T171del, I173del, and P174del and a two-amino-acid deletion, R165_T167delinsP, occurred in the omega loop, increasing the flexibility of the binding cavity. This rare collection of mutations has significance, allowing exploration of the diverse evolutionary trajectories of beta-lactamases and as potential future mutations conferring high-level ceftazidime resistance on isolates from clinical settings, compared with amino acid substitution mutations.