MULTIPLE MECHANISMS OF ACQUIRED 

 DRUG RESISTANCE 



Margaret J. Thornley, Jehudith Sinai 

 AND John Yudkin 



Queen Elizabeth College, University of London 



There are two possible ways of reconciling the different 

 theories which have been suggested for the origin of drug 

 resistance. The first is that the different mechanisms occur 

 in different micro-organism-drug systems. The second is that 

 the different mechanisms may occur in a single system and 

 that the different theories derive from different experimental 

 approaches. 



We have attempted to demonstrate the latter possibility in 

 the system Escherichia co/i-proflavine. We began with the 

 usual type of experiments on "training" and "reversion". 

 Each culture so produced was tested against a range of con- 

 centrations of proflavine, so as to measure its distribution of 

 resistance. In a culture grown in broth from a single cell in 

 the absence of drug, there was a slight increase in the propor- 

 tion of resistant cells during the first few subcultures. 



"Training*' and "Reversion" 



When grown even once in the presence of drug there w^as a 

 great increase in the number of resistant cells, able to grow in 

 much higher concentrations. Cultures derived from different 

 single cells gave significantly different numbers of resistant 

 cells after the same number of subcultures in the same drug 

 concentration. 



After subculture in the presence of drug, repeated sub- 

 cultures were made in the absence of drug. The degree of 

 reversion depended on the number of subcultures in drug, 

 on the concentration of the drug, on the strain of organism 



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