CHEMOTHERAPEUTIC AGENTS I5I 



xanthine, serine and thymine [21]. Other effects of the 

 sulphonamides have been reported, but whether they are 

 also the outcome of interference with reactions involving 

 PAB is not always known, e.g. sulphathiazole appears to 

 interfere with protein synthesis in Staph, aureus, but since 

 protein synthesis involves a complex metabolic sequence of 

 reactions, it is not possible to deduce whether this is a 

 direct effect or simply due to disturbances in the synthesis 

 of amino-acids or nucleotides [5]. It has been shown that 

 the even- but not the odd-numbered T phages are unable to 

 multiply in Esch. coli growing in media containing sul- 

 phanilamide together with methionine, serine, xanthine and 

 thymidine [19]. The results of these and other experiments 

 require to be interpreted with care, e.g. Pfiffner and his co- 

 workers have isolated from bacteria compounds of the 

 vitamin B^g group which contain adenine instead of di- 

 methylbenzimidazole, and Davis later found that these 

 substances (pseudo-Big) replaced B^g i^i all respects for 

 Esch. coli mutants requiring this vitamin or methionine. 



Antibiotics 



Though the precise details are still unknown, it is highly 

 probable that the sulphonamides owe their activity to the 

 fact that they are metabolic analogues. On the other hand, 

 no such simple hypothesis is available to explain the activity 

 of any of the antibiotics. There is no conclusive evidence 

 that penicillin inhibits enzyme systems concerned in respira- 

 tion or fermentation, and it is therefore unlikely that any 

 of the results described below are attributable to direct 

 interference with energy metabolism. By way of contrast, 

 aureomycin resembles 2:4-dinitrophenol and sodium azide 

 in that it may act as an uncoupling agent and prevent the 

 production of energy-rich phosphate groups [15]. If peni- 

 cillin (o-i-io Oxford Units /ml.) was added to growing 

 cultures of Staph, aureus, then within an hour of contact 

 with the antibiotic the ability of the organism to accumulate 

 amino-acids and synthesize protein progressively declined 

 [8]. Penicillin had no effect on the uptake, of glutamic acid 

 and lysine by washed suspensions of normal cells, hence it 

 II 



