BIOCHEMICAL ANTAGONISM 



centration which was effective against thiamin-rcquiring microorgan- 

 isms. Another type of manifestation of the correlation of action with 

 requirement for the metaboUte preformed in the medium was seen 

 with phenyl pantothenone acting on bacteria and yeasts. This com- 

 pound is the one obtained by exchanging — CO — CeHs for the COOH 

 of pantothenic acid. It inhibited the growth of all microbial species 

 tested irrespective of their pantothenic acid requirements. However, 

 its effect was reversed by pantothenic acid only in the case of those 

 organisms which needed the vitamin. For the other species, panto- 

 thenic acid was without effect in reversing the action of the agent. 

 An analogous situation has been recorded in animals, where gluco- 

 ascorbic acid caused scurvylike conditions in rats and mice, species 

 not requiring dietary ascorbic acid, and in guinea pigs, animals that 

 do demand a dietary source of the vitamin. Ascorbic acid failed to 

 cure the condition in the former species, but was quite active in this 

 respect for the latter. 



Thus far, only one instance of the correlation of effectiveness 

 with requirement for the related vitamin is known in the animal 

 world. 3-Pyridinesulfonic acid exhibited no action on mice, a species 

 not needing nicotinic acid in the diet, while it was quite effective in 

 killing nicotinic-acid-deficient dogs, and harmless in equal doses in 

 normal dogs. 



In contrast to these correlations, several of the metabolite 

 analogues have been found to be effective against most types of micro- 

 bial growth regardless of whether or not the related metabolite was a 

 nutritive essential. This was true of sulfanilamide, the analogue of 

 /)-aminobenzoic acid, and of benzimidazole, the analogue of the 



purines. 



These correlations of action with requirement pose an interesting 

 problem. Why is it that an organism which obtains its vitamins 

 externally is susceptible to the antagonistic analogue while the one 

 which produces its metabolite internally is usually resistant? In 

 other words, why does the ability to synthesize the metabolite make 

 the organism resistant to the deficiency disease caused by the analogue? 

 In only a few instances can this be said to result from formation of the 

 metabolite in amounts sufficient to negate the inhibition. A very small 

 beginning has been made on this problem with pyrithiamin. It has 

 been shown that the types of bacteria which were resistant to pyri- 



361 



