ANTISEPTICS 



153 



reaction of the drug with some cell constituents which 

 are more directly related to growth or cell division. 



The first attempt to explain sulfonamide action on 

 bacteria as a direct effect on the growth mechanism is 

 probabl}^ that by Mcintosh and Whitby (1939) who stated : 

 ''Sulfonamide drugs are not simple germicides. They 

 probably act by neutralization of some metabolic func- 

 tion or enzymatic activity". This idea was elaborated 

 by Wood (1940) who observed that the effect of sulfan- 

 ilamide is counteracted by p-amino benzoic acid. This 

 compound, which is found in small amounts in peptone 

 and meat extract, is necessary for the formation of cer- 

 tain indispensable cell constituents. Many bacteria can 

 synthesize it. Those species w^hich produce it freely, 

 e.g., bacteria of the colon grouj), are able to tolerate 

 large doses of sulfonamides. Resistant variants of sen- 

 sitive species have been shown to produce greater amounts 

 of p-amino benzoic acid than their parent strains (Landy 

 and assoc, 1943). 



All sulfonamides are "antagonized" by p-amino ben- 

 zoic acid, and this antagonism can be explained in sev- 

 eral ways : 1. The sulfonamide may combine with p-amino 

 benzoic acid and make it unassimilable. (That explan- 

 ation, however, has been disproved.) 2. The sulfonamide 

 may interfere with that part of the cell which synthe- 

 sizes p-amino benzoic acid. 3. On account of the great 

 similarity of the two compounds, the synthetic mechan- 

 ism of the cell may use sulfanilamide instead of p-ummo 

 benzoic acid and build it into cell structures which then 



