TH I AM INF 695 



bromide, (the analogue of thiamine having a pyridine ring instead of the 

 thiazole ring) , slightly inhibited the growth of Phy corny ces blakesleeanus, 

 which requires thiamine or its pyrimidine and thiazole components for 

 growth. However, the inhibition was reversed by the addition of the 

 thiazole component, which indicated that this organism is able to cleave 

 the pyrithiamine molecule and use the pyrimidine component. This in- 

 terpretation was supported by the fact that in low concentration, this 

 analogue stimulated the growth of Pythiomorpha gonapodioides, which 

 requires only the pyrimidine component of thiamine. Large amounts of 

 the analogue were toxic, but this effect could be overcome by the addition 

 of the pyrimidine or the thiazole component of thiamine. 



Woolley and White 32a found that pyrithiamine competitively inhibited 

 the growth of a number of organisms which require an external supply 

 of thiamine or its components, whereas it was without effect on organisms 

 which did not require thiamine. Those species which required intact 

 thiamine were about ten times as sensitive as those which needed only 

 the pyrimidine portion of thiamine, and about one hundred times as 

 sensitive as those stimulated by the pyrimidine and thiazole components 

 of thiamine. The pyrithiamine inhibition indices for Endomyces vernalis 

 and Mucor ra?nannianus were 130 and 800, respectively, but these or- 

 ganisms were not inhibited by 2-methyl-3-(/?-hydroxyethyl) pyridine, 

 even in concentrations as high as 100 y per cc. The resistance of the 

 organisms which do not require thiamine could not be attributed to their 

 synthesis of abnormally large amounts of thiamine since there was no 

 significant increase in the synthesis of this vitamin when the organisms 

 were grown in the presence of pyrithiamine. Subsequently, Woolley 76 

 reported that a new strain of Endomyces vernalis was obtained by grow- 

 ing a culture in media containing pyrithiamine; it was not inhibited by 

 twenty-five times the concentration of pyrithiamine which produced 50 

 per cent inhibition in the parent strain. It still required thiamine or its 

 pyrimidine portion as a growth factor, but it was able to utilize small 

 amounts of the pyrithiamine also. It appears that resistance to inhibition 

 by pyrithiamine may depend in part on the ability of the organism to 

 cleave the molecule into its pyrimidine and pyridine components, since 

 the latter does not interfere with the growth of organisms which are 

 inhibited by pyrithiamine. 



Wyss 77 reported that the pyrithiamine inhibition indices for Staphy- 

 lococcus aureus and Escherichia coll were 700 and 20,000, respectively. 

 When injected into mice in concentrations which were not toxic to the 

 animals, pyrithiamine was not anti-bacterial in the blood. Dreiser, 

 Scholtz and Spies 7S reported that pyrithiamine is inhibitory to the growth 



