Selection of variants of the TEM-1 β lactamase, encoded by a plasmid of clinical origin, with increased resistance to β-lactamase inhibitors

Abstract

A TEM-1 derived variant β lactamase with increased resistance to β lactamase inhibitors was selected in vitro. The variant β lactamase was obtained from the parent strain Escherichia coli J62-₂ containing resistance plasmid R1 which encodes the TEM-1 β lactamase. The variants were obtained by repeated subculture of E. coli J62-₂ (R1) for five days in the presence of sub-inhibitory concentrations of amoxycillin plus clavulanic acid. Comparison of this variant β lactamase with a clinically isolated TEM derived β lactamase, with increased resistance to β lactamase inhibitors, suggests that they are the same enzyme. Both β lactamases have the same pI at 5·25 and have similar ID₅₀ values for the β lactamase inhibitors clavulanic acid, sulbactam and tazobactam.