TEM-1 and TEMpUC19 β-lactamases can gain activity against ceftazidime and other expanded-spectrum cephalosporins via point mutation. The frequency of emergent resistance to ceftazidime at 4 × MIC was elevated ≥250-fold in hyper-mutable, MutS-deficient Escherichia coli harbouring these β-lactamase genes on high- or low-copy plasmids. Moreover, although ceftazidime-resistant mutants, or those with reduced susceptibility, were selected in both the wild-type and mutS hosts, many more mutants in the mutS host showed ceftazidimase-type extended-spectrum β-lactamase (ESBL) activity. This correlated with a G-A point mutation at position 484 in the blaTEM-1 and blaTEM-pUC19 genes, conferring the Arg164His amino-acid substitution found in the TEM-29 ESBL. Non-ESBL mutants lacked changes in blaTEM.
Bibliographical noteFunding Information:
The authors wish to thank R. Lloyd for the gift of E. coli strains, B. Bridges for discussions, and the UK Department of Health for financial support (grant no. 91 of the Resistance to Antibiotics and other Antimicrobial Agents Research Programme). This work was presented, in part, at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (Washington, DC, 2004) and the 15th European Congress of Clinical Microbiology and Infectious Diseases (Copenhagen, 2005).
- Escherichia coli
- Extended-spectrum β-lactamase