Multiple Mechanisms of Drug Resistance 153 



Table II 



Induction by proflavine 1 /ig./mt.. for 10 days in non-dividing cells of 



Escherichia coli R„ 



in the number of cells induced and in the level of resistance 

 achieved (Fig. 7). No induction occurred at 5° or 20°, or 

 when the cell density was low, or in the absence of tap water. 

 It was found that the presence of proflavine for only two days 

 was enough to give a substantial rise in the number of resistant 

 cells when they were suspended in the absence of proflavine 

 during the following 7 days (Fig. 8). Induction resulted not 

 only in a considerable rise in numbers of cells with pre- 

 existing levels of resistance, but also in the emergence of cells 

 of much higher resistance which previously were not present. 

 During the induction, there was initially a considerable fall 

 in the number of viable cells, which then increased. We 

 believe that cells become temporarily non-viable whilst under- 

 going induction. The induced cells retained their resistance 

 when subcultures were made in the absence of drug. They 

 were cross-resistant to chloramphenicol and aureomycin. In 

 these ways, and in the much higher levels of resistance 

 achieved, these cells differed from those in which increased 

 resistance (phenotypic adaptation) occurred during growth 

 when small amounts of proflavine were added. 



