1948] 



ORIGIN OF BACTERIAL RESISTANCE TO ANTIBIOTICS 



69 



first-step penicillin-resistant strains (Demerec, 19456) is slight as compared with 

 the variability observed among first-step streptomycin-resistant strains. 



10' 



10 



10 



CO 



or 

 > 10 



> 

 cr 



3 

 CO 



cr 



UJ 



CD 



§ io : 



z 



10' 



10 



.1 .2 .3 .4 .5 .6 .7 .8 .9 1.0 U 12 13 1.4 15 

 PENICILLIN CONCENTRATION' OXFORD UNITS PER ML 



Figure S. Stepwise build-up of resistance to penicillin in S. aureus. Fir6t from left, 

 survival curve of stock culture; second, survival curve of first-step resistant strain isolated 

 from a colony of the stock culture growing on the concentration indicated by the arrow. 

 The other curves are of second-, third-, and fourth-6tep resistant strains isolated from 

 colonies growing on the concentrations indicated by the arrows. 



In the build-up of resistance to streptomycin, resistant strains of the second 

 step, third step, etc., showed behavior similar to the first-step strains; that is, 

 they exhibited a wide range of variability in degree of resistance. By plating 

 bacteria of a low-resistance first-step strain on a concentration of streptomycin 

 that is sublethal for that strain, one can isolate second- step resistant strains that 



85 



