88 M. R. Pollock 



directly. However, there is every reason to believe that were 

 it not for this rapid induction, 569 would be highly sensitive 

 to penicillin; and this conclusion is supported by the rela- 

 tively low penicillin resistance of the non-inducible double 

 mutant strain 569/H/l derived from 569/H. In the absence 

 of penicillin, 569/H/l produces 15 times as much enzyme as 

 569; 569/H/l is however strictly non-inducible so that, after 

 addition of penicillin, 569 forms penicillinase approximately 

 25 times as fast as 569/H/l. It is therefore not difficult to 

 understand why 569 can develop in concentrations of peni- 

 cillin up to 30 times the highest levels permitting growth of 

 569/H/l. The significance of enzyme induction as a means of 

 developing specific drug resistance is that it is (usually) adap- 

 tive and therefore economical. At the expense of a slightly 

 lower penicillin resistance than 569/H, 569 avoids using up to 

 1 per cent of its protein-synthesizing ability on a normally 

 useless enzyme — except under just those conditions where that 

 enzyme is essential for survival. It should be noted that 

 enzyme induction may also contribute to the development of 

 drug resistance (of a genetically more stable type) by per- 

 mitting survival and multiplication of cells after addition of 

 the drug and so increasing the possibility of mutations towards 

 higher resistance (e.g. constitutive mutants, or mutants with 

 more efficient induction systems). 



The difPerence in penicillin resistance of 5/B and 569/H, 

 whose rate of total penicillinase production is the same, may 

 possibly be due to the very much larger amount of intra- 

 cellular enzyme [" y-penicillinase " : see Pollock (1956^)] 

 present in the latter. 



These two strains have been referred to respectively as 

 "magno-" and "pleno-" penicillinase-constitutive types. 

 There is really nothing apart from their origin to justify such 

 a distinction. It was made with the intention of emphasizing 

 that the pleno-constitutive strain 569/H was derived from an 

 inducible parent strain which was able to undergo a series of 

 mutations involving different increases in the quantity of 

 basal enzyme. The semi-constitutive strain 569/A which still 



