EFFECTS ON FUNGI AND YEASTS 571 



together, at concentrations which inhibit only slightly when each is present 

 alone, block growth completely; this was interpreted by Kiesow (1960 b) 

 to mean that the quinone form of menadione is active, since ferricyanide 

 is able to reoxidize menadiol as it is formed, but there are other possible 

 explanations, and even if it is true it does not indicate the mechanism by 

 which menadione inhibits. 



Mechanisms of Antifungal Action 



The growth of Phycomyces blakesleeanus in a synthetic medium is inhib- 

 ited by menadione, and this inhibition is reversed by the addition of nico- 

 tinate, nicotinamide, or various possible precursors of these (e. g., anthra- 

 nilate, 3-hydroxyanthranilate, indole, kynurenin, and tryptophan) (Schop- 

 fer and Boss (1948). When this organism is grown with menadione there 

 occur some interesting changes in the levels of certain cofactors, as deter- 

 mined by analysis of the thalli and medium (Schopfer and Boss, 1949). 

 Some cofactors rise and some fall, and the relationship to menadione con- 

 centration is very puzzling (see accompanying tabulation). The interference 



with the synthesis of pyridine nucleotides may be one major mechanism 

 of the growth inhibition, since the most potent reversers are nicotinate, 

 nicotinamide, and NAD, but disturbances in the other cofactors must also 

 play a role. Thiamine was added to the medium and menadione increased 

 its destruction; 49% was lost in the control, 67% in 0.012 mM menadione, 

 and 73% in 0.048 mM menadione. Bisceglie (1951) also reported that 2,3- 

 dichloro-l,4-naphthoquinone at 0.00044 mM or lower markedly inhibits 

 the formation of nicotinate in Deuterophoma tracheiphila, a phytopathogenic 

 fungus, and moderately depresses the synthesis of riboflavin and folate. 

 Furthermore, certain amino acids, e. g., arginine, tryptophan, proline, and 



