INHIBITION OF BETA-LACTAMASE SYNTHESIS IN STAPHYLOCOCCUS-AUREUS BY MINOCYCLINE

The effect of minocycline on .beta.-lactamase synthesis in Staphylococcus aureus was examined. Some inhibition of synthesis was detectable in organisms exposed to 0.015 mg minocycline/liter (0.15 of the single cell MIC) and complete inhibition was observed at 0.05 mg drug/liter (0.5 MIC). In contrast, total cell protein synthesis was less susceptible to inhibition by minocycline. Although synthesis of .beta.-lactamase was inhibited by low concentrations of minocycline, benzylpenicillin and minocycline failed to show synergy when tested in a variety of combinations against penicillinase producing staphylococci. In fact, benzyl-penicillin did not influence the minocycline MIC, and in the majority of cases the same pattern was exhibited by minocycline, i.e., it did not generally alter the penicillin MIC. This is an example of true indifference whereby each antibiotic behaves as if the other were not present. The results presented here are discussed in relation to the possibility of therapeutic control of .beta.-lactamase producing organisms by suppressing the level of enzyme produced.