Drug Resistance in Bacteria 15 



at which "training" has been carried out. A good example 

 of this type of behaviour is found with Bad. lactis aerogenes 

 and proflavine and it is easily explained on an adaptive 

 theory involving an automatic adjustment of the enzyme 

 systems in the cells in response to the environment (Davies, 

 Hinshelwood and Pryce, 1945; Dean, 1955). The alternative 

 is to assume a complex polygenic system — a theory which 

 encounters difficulties when the resistance of colonies picked 

 from proflavine plates is re-tested. It is found that resistance 

 or non-resistance on re-test depends on the buffering capacity 

 of the agar medium in the primary plating. Since proflavine 

 is antagonized by the acids produced by growing cells, a simple 

 explanation of a non-genetic nature can be given. It is that on 

 the lightly buffered plates cells which have just begun to 

 adapt to proflavine will de-adapt when the acid antagonizes 

 the drug and hence on re-test would be expected to be no more 

 resistant than in the primary test. On the well buffered plates, 

 however, the acids produced by the growing cells will not be 

 present in sufficient amount to change the pH of the medium 

 and hence no considerable antagonism of the drug or de- 

 adaptation will take place (Dean and Hinshelwood, 1955). 



Accelerated Adaptation to Drugs 



It has been shown that if proflavine is added gradually to 

 an actively growing culture of Bad. ladis aerogenes the cells 

 can be rapidly adapted to grow in concentrations of drug 

 which if added directly to the culture would cause long lags 

 or even cessation of growth. Using this method Baskett 

 (1952) was able to adapt cells of Bad. ladis aerogenes to 

 110 mg./l. of proflavine in 220 minutes, a time interval too 

 short for an appreciable selection of pre-existing proflavine- 

 resistant mutants in the culture. 



Dean (unpublished) has carried out similar experiments 

 with Bad. ladis aerogenes and proflavine and sodium azide. 

 Any pH changes in the medium were carefully followed since 

 both proflavine and azide would be expected to be less active 



