154 AXTISEPTIC8 



fail to function because of the abnormal sulfone side- 

 chain. This would cause a retardation of growth propor- 

 tional to the number of abnormal side-chains per cell, 

 and eventually a complete cessation of growth. The 

 compounds thus incapacitated may include enzymes, but 

 the decrease of enzymatic activity would be the result 

 rather than the cause of abnormal growth. 



The delayed action of sulfonamides can be explained 

 by postulating a certain store of ^^-amino benzoic acid 

 in the cell. The sulfonamide cannot retard growth until 

 this store is exhausted. The results of Fig. 30 agree 

 well with the assumption that the new cells are accumu- 

 lating increasing numbers of inactive, or one might say, 

 defunct molecules. 



A very interesting parallel to the above case has been 

 obtained with the sulfone derivative of nicotinic acid. 

 Mcllwain (1940) tested the action of pyridine sulfonic 

 acid amide on bacteria which need nicotinic acid amide. 

 The compound retarded the growth of staphylococci, and 

 this effect could be counteracted by nicotinic acid amide, 

 just as that of sulfonamides is counteracted by p-ammo 

 benzoic acid. In a later publication (1942) he gave as 

 further example of this phenomenon the counteraction of 

 a-amino sulfonic acids by a-amino carboxylic acids in 

 Proteus, and of acriflavine by amino acids in Bad. coli. 

 The above explanations are often presented in various 

 forms. Johnson (1942) considered all of them improb- 

 able because one molecule of p-amino benzoic acid is 

 suJBficient to neutralize the effect of 23,000 molecules of 

 sulfanilamide on luminescent bacteria. 



Fox and Rose (1942) explained this ratio as resulting 

 from the ionization of sulfonamides, the small disso- 

 ciated fraction only being effective. They tested the 

 minimum growth-retarding dose of the drug at pH 7, and 

 the minimum dose of p-sHinmo benzoic acid which would 

 neutralize the effect. The ratio obtained varied greatly 

 from one to the other of the four sulfonamides tested, aa 



