PENICILLIN-INDUCED RESISTANCE TO 

 PENICILLIN IN CULTURES OF BACILLUS CEREUS 



M. R. Pollock 



National Institute for Medical Research, Mill Hill, London 



Although the mechanisms of drug resistance in bacteria 

 are, in general, not well understood, there are certain strains 

 whose ability to multiply after addition of penicillin can be 

 confidently ascribed to their production of an enzyme, peni- 

 cillinase, which hydrolyses the drug to the antibiotically 

 inactive penicilloic acid. This is true for the naturally occurring 

 penicillin-resistant staphylococci (Barber, 1953) and several 

 different species in the Bacillus genus. This report is concerned 

 solely with the mechanism of the development of this peni- 

 cillinase-type of penicillin resistance in cultures of Bacillus 

 cereus, and it will be shown that the change can take place 

 in two quite distinct ways, both of which require the addition 

 of penicillin for their full expression. In both mechanisms, 

 the change involves a purely quantitative increase in the 

 ability to form a single, enzymically active protein. Such a 

 relatively simple system naturally lends itself to a more de- 

 tailed and more accurate analysis at the biochemical level 

 than most types of drug resistance. 



In the first mechanism, the resistance is acquired by the 

 process of enzyme induction. A greatly increased rate of 

 penicillinase formation can be very rapidly acquired, within 

 the space of a few minutes, in all or most of the individual 

 cells in the population by brief contact with low concentra- 

 tions of penicillin (1 unit/ml. or less). This acquired ability 

 to produce penicillinase at increased rate is biochemically 

 stable but is not inherited by daughter cells as a genetically 

 stable character, being gradually lost as the cells grow in the 

 absence of the antibiotic. After 7 to 12 generations the popu- 



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