D. W. WOOLLEY 



inhibited growth competitively with nicotinic acid, thiopanic acid with 

 pantothenic acid, pyrithiamin with thiamin, benzimidazole with 

 adenine or guanine, 2,4-diamino-7,8-dimethyl-10-ribityl-5,10-dihydro- 

 phenazine and 6,7-dichloro-9-ribitylisoalIoxazine with riboflavin, 

 and desthiobiotin with biotin. Many of these examples, along with 

 others, will be brought into the discussion later to illustrate general 

 deductions. In every instance, the inhibitory action of the analogue 

 was negated by increasing the amount of the metabolite in the basal 

 medium. Therefore it could be said that the action of the analogues 

 was in some degree due to the production of deficiencies of the metabo- 

 lites. In this respect, however, the bacterial examples lacked some 

 of the force of the animal demonstrations since, in the latter cases, it 

 was possible to examine the specific anatomical and physiological 

 changes characteristic of various vitamin deficiencies which were 

 produced by the agents. 



One feature of the action of antagonistic structural analogues 

 of metabolites on a wide variety of living things, both animal and 

 microbial, has been the marked species specificity shown by some of 

 these agents. With several of the compounds, inhibitory action was 

 manifest only against the species for which the metabolite concerned 

 was an essential growth factor. Against those species which syn- 

 thesized their own supply of the metabolite in question, the analogue 

 was ineffective. Thus, thiopanic acid was able to inhibit only those 

 bacteria that required pantothenic acid, and was ineffective in pre- 

 vention of growth of species not needing this vitamin. A somewhat 

 similar situation obtained with 3-pyridinesulfonic acid in relation to 

 propagation of organisms requiring nicotinic acid. With pyrithiamin, 

 the dependence of inhibition on the type of thiamin requirement was 

 highly developed. Species which demanded the intact vitamin for 

 growth were inhibited by minute amounts of pyrithiamin; those 

 which were content with the pyrimidine portion alone of the vitamin 

 could be prevented from multiplying only by ten times the amount 

 which was eff"ective with the former organisms; and those species 

 which used both pyrimidine and thiazole portions of thiamin needed 

 a further tenfold increase in the concentration of analogue. Those 

 species capable of good growth in the absence of thiamin or of its 

 component parts were quite resistant to any action of pyrithiamin, 

 and were able to thrive in media containing a million times the con- 



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