Multiple Mechanisms of Drug Resistance 151 



variation in resistance but a variation in adaptability. If 

 this is so, then the addition of proflavine to a synchronized 



60 I20 ISO 60 I20 180 60 I20 I80 60 I20 ISO 60 I20 ISO 



Time (mins) 



Fig. 6. Effect of proflavine 4 (i.g./ml. on increase in resistance 

 and growth inhibition when added at different times of a division 

 cycle in a synchronized culture of Esch. coli 36. 



1 — proflavine added at once at 24 min. after returning the 



culture to 37°C 

 2 — proflavine added at once at 56 min. after returning the 



culture to 37°C 

 A — total viable count 

 B — cells resistant to 5 [jLg./ml. proflavine 

 C — cells resistant to 5-7 [jig./ml. proflavine 

 D — cells resistant to 6-2 [i.g./ml. proflavine 

 E — cells resistant to 10 ptg./ml. proflavine 



O — normal colonies 4 y.g.fm\. proflavine present 



# — small colonies no proflavine present 



Time from end of cooling. 



culture should result in no increase in resistance at some 

 stages and a significant increase at other stages. This predic- 

 tion we have confirmed experimentally (Fig. 6). 



