Staphylococcal penicillinase and the new penicillins

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Abstract
The results of an investigation of staphylococcal penicillinase, the induction of the enzyme by several new penicillins and its enzymic activity towards them are presented. The enzyme has a pH optimum of 5-8 and a temperature optimum of 55[degree]. The continuous presence of inducer is required for the induction of this enzyme unlike the penicillinase of Bacillus cereus. Induction by 2,6-dimethoxyphenylpenicillin is readily demonstrable because its hydrolysis by the enzyme is very slow. Induction by 4 rapidly hydrolysed penicillins is much more difficult to observe; it is probable that they are all good inducers because uninduced cells of Staphylococcus aureus are almost as resistant to each drug as are fully induced cells. Measurement of Michaelis constants (K[image]) revealed that effectiveness against penicillinase-producing staphylococci of the penicillins studied is an inverse function of their affinity for the enzyme. 2,6-Dimethoxyphenylpenicillin with a Km of 28 m[image] is by far the most effective; 4 others, with K[image] values of 2-5-17 [mu][image] are largely ineffective. The Km of staphylococcal penicillinase for 2-5 [mu][image] -penicillin G is considerably lower than that of other penicillinases. Staphylococcal penicillinase is usually partly free and partly bound to the cells. Comparison of Km values for free and bound enzyme revealed differences which might be accounted for by an accessibility barrier between bound enzyme and substrate. Among the various new penicillins, 3 important biological properties (affinity for the enzyme, antimicrobial activity and ability to induce the enzyme) all varied independently. High affinity for the active enzyme was not required of its inducer.