Non-naturally occurring mutants of TEM-17 (E104K), TEM-12 (R164S) and TEM-26 (E104K:R164S) extended-spectrum (ES) β-lactamases bearing threonine at position 237 were constructed by site-specific mutagenesis and expressed under isogenic conditions in Escherichia coli. Quantification of β-lactamase activities and immunoblotting indicated that Ala-237 → Thr did not significantly affect expression levels of these ES enzymes. Minimum inhibitory concentrations of β-lactam antibiotics showed that the presence of threonine at position 237 exerted a dominant effect increasing the enzymes' preference for various early generation cephalosporins over penicillins. Activity against broad-spectrum oxyimino-β-lactams was also changed. The effect of Ala-237 → Thr on the activity against ceftazidime, aztreonam, cefepime and cefpirome of all three ES TEM enzymes was detrimental. Introduction of Thr-237 improved activity against cefotaxime and ceftriaxone in TEM-12 and TEM-26, but not in TEM-17. © 2001 Federation of European Microbiological Societies.
Giakkoupi, P., Hujer, A. M., Miriagou, V., Tzelepi, E., Bonomo, R. A., & Tzouvelekis, L. S. (2001). Substitution of Thr for Ala-237 in TEM-17, TEM-12 and TEM-26: Alterations in β-lactam resistance conferred on Escherichia coli. FEMS Microbiology Letters, 201(1), 37–40. https://doi.org/10.1016/S0378-1097(01)00239-7