272 Mary Barber 



that the laboratory strains show an associated diminution in 

 growth rate and coagulase and a-toxin production, and have 

 a lower order of resistance. 



The loss in properties usually associated with pathogenicity 

 may be a laboratory phenomenon, which would not occur in 

 vivo. It may, however, be of greater significance. Staphylo- 

 coccal infections have sometimes yielded penicillin-sensitive 

 Staph, aureus in association with penicillinase-producing 

 staphylococci which are coagulase-negative. Moreover, 

 Rountree (1956) studied staphylococci isolated from the 

 anterior nares of 120 people in the Wabag region of New 

 Guinea, an area where penicillin has not yet been widely used, 

 and found that none of 23 strains of Staph, aureus was resist- 

 ant to penicillin, whereas 18 out of 110 coagulase-negative 

 staphylococci were penicillinase producers. 



Although, at present, the strains isolated in the laboratory 

 have only very weak penicillin-destroying activity this has 

 increased during the course of the experiments, and with 

 further prolonged exposure to penicillin might approach that 

 of the clinically isolated strains. If so, our views on the 

 mode of origin of penicillin-resistant staphylococcal infection 

 may need modification. Sub-bacteriostatic concentrations of 

 penicillin in the tissues or abscesses of patients treated with 

 penicillin must be very common, and transfer of strains of 

 Staph, aureus from patient to patient where this is the case 

 may well constitute a method of passaging strains in the 

 presence of very small concentrations of penicillin, similar to 

 those used in this study. It is also pertinent to note that 

 penicillin-resistant staphylococcal infection was uncommon 

 until the antibiotic had been in widespread use for several 

 years. 



It appears possible, therefore, that the penicillinase of 

 staphylococci is an adaptive enzyme for the production of 

 which very prolonged exposure to the substrate is necessary. 

 Even if this is so, however, spontaneous mutation leading to 

 the emergence of cells better able to produce the enzyme 

 almost certainly takes place, and this, together with selection, 



