METABOLITE ANTAGONISTS 231 



in Fig. 48 indicate that A. niger synthesizes either p-aminobenzoic acid 

 or some other compound which reverses the inhibitory action of sulfa- 

 nilamide. When p-aminobenzoic acid was added to the medium, sulfa- 

 nilamide no longer inhibited the growth of yl. niger (Hartelius and Roholt, 

 1946). Other fungi have been shown to react like A. niger when cultured 

 in media containing sulfanilamide (Fourneau et al., 1936). 



It has been assumed that self-sufficient fungi require the same vitamins 

 as the deficient species. The synthesis of a vitamin may suggest its 

 need but does not demonstrate it. Antivitamins (or other antimeta- 

 bolites) provide a way of demonstrating the need of self-sufficient fungi 

 for the vitamins they synthesize. Thus A. niger requires p-aminobenzoic 

 acid just as Rhodotorula aurantica does, but this need can be demonstrated 

 only in the presence of a specific reversible inhibitor such as sulfanilamide. 

 This technique offers a possible way of discovering new vitamins and 

 other metabolites. If a compound inhibits growth, it is worth while to 

 search for compounds which overcome this inhibition reversibly. 



For most purposes sulfanilamide has been replaced by other sulfona- 

 mides. However, sulfanilamide appears to be the most active sulfona- 

 mide against fungi. For a review of the clinical aspects of the sulfona- 

 mides in mycoses and for literature citations, see Wolf (1947). 



Stoddard (1947) has reported the sulfonamides to be of some value in 

 controlling the X disease of peach (a virus). Addition of p-amino- 

 benzoic acid lessened the effectiveness of the treatment. 



It is recognized that the simple Woods-Fildes theory of competitive 

 inhibition is inadequate to explain completely the mechanism of sulfona- 

 mide therapy. In vivo the environment is much more complex than in 

 simple laboratory media. For further information and references to the 

 literature, see Sevag et al. (1945) and Mudd (1945). 



Thiamine antagonists. Thiamine may be inactivated by an enzyme, 

 thiaminase, which is found in fish viscera (Sealock et al., 1943) and prob- 

 ably occurs in other organisms. Foxes which are fed raw fish may 

 develop a thiamine-deficiency disease (Chastek paralysis). The mode of 

 inactivation was further investigated by Krampitz and Woolley (1944), 

 who found that thiamine was destroyed by a process of enzymatic hydrol- 

 ysis whereby the thiazole and pyrimidine moieties were formed. Mucor 

 ramanniamis (thiazole-deficient) and Endomyces vernalis (pyrimidine- 

 deficient) were used as test organisms in the preliminary work. Another 

 thiamine antagonist of unknown nature has been reported to occur in 

 bracken fern (Weswig et al., 1946). 



Pyrithiamine, an analogue of thiamine, has been used in studies of 

 competitive thiamine inhibition. Unfortunately, the exact structure of 

 this compound is not known. In papers published before 1949 it was 

 assumed that pyrithiamine had the structure now assigned to neopyri- 



