The Acquisition of Penicillin Resistance by Staphylococcus aureus, Strain Oxford

SUMMARY: The Staphylococcus aureus strain known as Staph. Oxford (NCTC 6571) produces, in any one mutational step towards penicillin resistance, a number of mutants, differing by various characteristics. One of these characteristics is the degree of penicillin resistance. The most resistant first-step mutant is about five times more resistant than the least resistant one. As such mutants are picked up from different penicillin concentrations, according to their higher or lower resistance, the resultant cultures may appear graded by the amount of penicillin present in the medium from which they were obtained. Mutants recognizable as members of one clone, however, show the same resistance from whatever concentration of penicillin they are isolated, within the range on which their growth is possible.

Another characteristic is the distribution of penicillin sensitivity in the population; it differs between mutant strains but, contrary to expressed views, the curves of distribution do not become flatter in mutants of increased resistance, provided one uses a logarithmic scale for the drug concentrations.

Prolonged culture on agar with sub-inhibitory concentrations of penicillin does not lead to increased penicillin resistance. In fluid medium with low penicillin concentrations, on the other hand, stable mutants, resistant to inhibitory concentrations, soon arise.

The growth rate of most penicillin-resistant strains is slower than that of the original strain, and is slowed down still further by the presence of penicillin, even by less than one-hundredth of the inhibitory concentration.

Variants and mutants of slightly increased penicillin-resistance are often pigmented.

Penicillin in sub-inhibitory concentrations enhances autolytic processes in the original organism and in all the mutants, and curious pictures of colony morphology are encountered which result from the interplay of autolysis and secondary growth.