Staphylococcal Penicillinase: A Study of Some Aspects of the Production of Staphylococcal Penicillinase and Its Association with Pathogenicity

SECTION I. This section takes the form of an introductory discussion. Some of the features of the resistance of staphylococci to penicillin due to penicillinase production and some environmental factors which may affect this resistance are reviewed. A brief mention is made of the new penicillin B.R.L. 1241, and finally some general aspects of the problem of estimating the pathogenicity of staphylococci are considered. SECTION II. This section gives an account of some experiments in the estimation of penicillinase activity both constitutive and inducible. The following points are made from the results. 1. Constitutive penicillinase activity within a strain varies from clone to clone. 2. In the absence of penicillin in the substrate the level of activity of each clone is relatively stable. 3. On solid media containing small concentrations of penicillin, very little if any induction of penicillinase activity takes place, but there is evidence that there is some selection of clones of higher constitutive penicillinase activity. 4. All clones of whatever constitutive level of penicillinase activity are inducible by large concentrations of penicillin to the same high level of activity. 5. Sensitivity to penicillin by the tube method seems to depend, with a large inoculum, on the total penicillinase inducibility of the cells. With a light inoculum it seems to depend more on the constitutive level of the penicillinase activity. With a very small inoculum, complete sensitivity comparable with the Oxford staphylococcus, is the rule. 6. It is suggested that in the human host, some relative selection may take place at certain penicillin concentrations of organisms with higher basic constitutive levels of penicillinase activity, without any great degree of penicillinase induction taking place. 7. The effect of antipenicillinase rabbit serum is shown in reducing the resistance of penicillinase producing staphylococci in certain concentrations of penicillin and with certain weights of inoculum. SECTION III. This section is concerned with the examination of a selection of clones isolated from each strain used in the previous section. These clones are distinguished only by their various degrees of penicillinase activity. Clones of low activity (L.A.) and high activity (H.A.) before induction, and the clones of high activity after induction (H.A.1.) are used. The pathogenicity and general biochemical activity of these clones is estimated using the following criteria, -coagulase, alpha haemolysin, delta haemolysin, fibrinolysin, hyaluronidase, deoxyribonuclease, lipase, phosphatase and antigen line production and pathogenicity to mice by intravenous inoculation. The following conclusions are reached: 1. No correlation is demonstrated between pathogenicity, general biochemical activity and penicillinase production, either as between the total populations of different strains or between fractions of the population within strains. 2. There is distinct correlation shown between antigen line, alpha haemolysin and delta haemolysin production and mouse pathogenicity as estimated quantitatively. 3. There is no correlation shown between any of the group mentioned above and coagulase, hyaluronidase, fibrinolysin, lipase or deoxyribonuclease production as estimated quantitatively