240 PHYSIOLOGY OF THE FUNGI 



DEVELOPMENT OF FASTNESS 



An organism which has become tolerant, or resistant, to an inhibitor 

 (analogue, drug, antibiotic, etc.) after exposure is said to be fast, or more 

 specifically pyrithiamine-fast, sulfanilamide-fast, or penicillin-fast, as 

 the case may be. Fastness is a very common phenomenon, although it 

 appears to have been but little studied in fungi. It is an important factor 

 which limits the use of many antibiotics and the sulfonamides in medicine. 

 This phase of fungus physiology deserves more attention than it has 

 received. It is conceivable that the prolonged use of a single fungicide 

 to control a fungus pathogen could lead to the development, or selection, 

 of a strain which would be relatively tolerant to the effect of the fungicide. 

 Such findings do not appear to have been reported from field studies, but 

 this possibility should be kept in mind. 



Fungi do become fast to various antagonists. WooUey (19446), by 

 repeatedly subculturing Endomyces vernalis in a medium containing 

 pyrithiamine, developed a strain which withstood twenty-five times the 

 concentration of pyrithiamine which served to reduce the growth of 

 the parent strain to half the maximum. In this instance, fastness was 

 correlated with the ability of the pyrithiamine-fast strain to cleave the 

 inhibitor molecule into its cyclic moieties. Thus, the development of 

 pyrithiamine fastness may be ascribed to the formation of an adaptive 

 enzyme which destroyed the antagonist. Escherichia coU, which is not 

 inhibited by pyrithiamine, also hydrolyzed this compound. These 

 results indicate that adaptive enzymes may play a role in the develop- 

 ment of fastness. 



In addition to resistance or fastness which develops in organisms cul- 

 tured in the presence of an inhibitor, it has been found recently that 

 various bacteria not only develop resistance but may develop strains 

 which are actually dependent upon the presence of the "inhibitor" before 

 they can grow. Yegian et al. (1949) have found that culturing Myco- 

 bacterium tuberculosis in the presence of streptomycin gave rise to strains 

 which were fast to this antibiotic and also produced strains which cannot 

 grow unless streptomycin is present in the medium. 



SUMMARY 



The normal utilization of a metabolite may be prevented or inhibited 

 in three ways: (1) destruction or removal in an unavailable combination 

 of a metabolite; the enzymatic hydrolysis of thiamine and the combina- 

 tion of biotin with avidin are representative examples of this mode of 

 inactivation ; (2) the noncompetitive inhibition of various enzymes by 

 such compounds as iodoacetate, cyanide, and azide; (3) competitive 

 inhibition due to metabolite antagonists. This type of inhibition is 



