Penicillin-induced Penicillin Resistance 83 



distinguishing 5/P colonies from those of 5/B, but cultures from 

 separate colony isolates were found to form penicillinase at 

 rates characteristic either of the 5/P or 5/B prototypes with 

 slight variation and no overlap (see Fig. 1). Since these 

 isolates were obtained from the same plate, it could hardly 

 be argued that 5/B colonies were simply examples of the 

 extreme limits of a wide variation normally shown by 5/P 

 clones, or vice versa. It could be confidently concluded that 

 they represented two distinct strains. If, therefore, there is 

 any clonal variation within populations of 5/P and 5/B of 



o ' 



in 



1 



Jj 



/•O 2-0 J-0 4-0 SO 



log specific penicillinase activity 

 pl./hr./mg. 



Fig. 1. Distribution of specific penicillinase activities amongst 



single-colony isolates of penicillin-resistant mutants from cultures 



of B. cereus 5. 



the continuous type postulated by Yudkin (1953) affecting 

 the rates of penicillinase formation by individual cells, it must 

 have very low genetic stability and/or a very narrow range 

 and would therefore be of little significance in the evolution 

 of a more resistant population. 



Addition of penicillin to cultures of members of the "5" 

 group causes no significant increase in rate of penicillinase 

 formation. This lack of inducibility is probably the explana- 

 tion of why it is easy (in comparison with the 569 group) to 

 exert differential selection pressure by growth in appropriate 

 concentrations of penicillin. 



It was at first thought that the 5— >5/B mutation involved 

 the acquisition of a completely new enzyme. However, 



