154 BACTERIOLOGICAL CHEMISTRY 



is found in the fact that pantoyltaurine resistant strains 

 of G. diphtherice can utilise 3 -alanine instead of panto- 

 thenic acid. If susceptible strains were grown in the 

 presence of large amounts of p-alanine, or were gradually 

 trained to do without pantothenic acid, it would be 

 expected that they would become resistant to pantoyl- 

 taurine and in fact this has been shown to take place. 

 The converse of this can also happen ; if 0. diphtherice 

 is repeatedly subcultured in media rich in pantothenic 

 acid it becomes progressively more exacting in its need 

 for pantothenic acid and at the same time more sus- 

 ceptible to pantoyltaurine. This behaviour is very 

 similar to that postulated by Knight to account for the 

 more complex demands of the parasitic organisms and 

 viruses as compared with those of saprophytic and 

 autotrophic bacteria (see Chapters VI and VII). In 

 general drug resistance, once acquired, is stable through 

 many generations of subculture on ordinary media. The 

 development of drug resistance by " training " appears 

 to take place in two stages. In the early stages the 

 resistance is easily reversed, does not survive continued 

 sub-culture on ordinary media, and is specific to the drug 

 used, related dnigs being active. The resistance is 

 probably due to the stimulation of a reserve, less efficient, 

 growth mechanism which is present in the organism 

 but normally plays only a minor role in metabolism. 

 In the early resistant phase it serves to tide over the 

 organism, until it has elaborated the final alternative 

 mechanism which confers permanent resistance on the 

 organism. This permanent mechanism may be a new 

 way of by-passing the mechanism normally inhibited by 

 the drug, or it may involve the development of an enzyme 

 system which can synthesise enough of an antagonist 

 to the drug to overcome its effects. 



The ease with which it is possible to produce resistance 

 to different drugs by " training " varies considerably. 

 Streptococci and staphylococci become readily resistant 





