ADAPTATION OF BACTERIA TO ANTIBIOTICS 257 



oxidation-reduction system, it is conceivable that actinomycin may be 

 reduced through the action of the vitamin. Such an effect should be 

 greatly increased under anaerobic conditions, where no reoxidation due 

 to atmospheric oxygen could occur. Twenty-five to 50 times as great a 

 neutralizing effect of ascorbic acid upon actinomycin was obtained un- 

 der anaerobic conditions with CI. butyrkum as a test organism as under 

 aerobic conditions with B. mycoides. Reduced actinomycin was inactive. 

 It was concluded, therefore, that the neutralizing action of ascorbic 

 acid upon actinomycin was due merely to its reducing properties. As far 

 as the common growth factors are concerned, the action of actinomycin, 

 like that of penicillin, differs from the mechanism proposed by Woods 

 (1032) and others for sulfanilamide inhibition. 



Among the phenomena of inhibition of antibiotic substances, the ac- 

 tion of cysteine offers some important practical applications. This sub- 

 stance inhibits the antibacterial action of penicidin (29), penicillin, cit- 

 rinin, gliotoxin, clavacin, pyocyanin (116), and streptomycin (327). 

 It was suggested that this is due to the fact that the mode of action of 

 certain antibiotics involves their ability to interfere with the normal 

 functions of the sulfhydryl groups in bacterial metabolism. The rate 

 of inactivation of penicillin was found (136) to be dependent on the 

 concentration of penicillin and on the fH of the medium j since thio- 

 glycolic acid was somewhat less effective and other amino acids, like 

 cystine and methionine, had no effect, it was suggested that the process 

 of penicillin inhibition involves both the sulfhydryl and the amino 

 groups of cysteine. Since i mg. of cysteine was sufficient to inactivate 

 about 270 to 410 O.U. of penicillin, it was suggested (423) that ad- 

 vantage be taken of this fact in testing for sterility of penicillin prepa- 

 rations. 



ADAPTATION OF BACTERIA TO ANTIBIOTICS 



Different strains of bacteria vary greatly in their susceptibility to the 

 same antibiotic substance (75). This is true particularly of penicillin 

 (267) and streptomycin (965). By growing an organism in media con- 

 taining increasing concentrations of the antibiotic, more resistant strains 

 can be obtained. The rate and degree of acquired resistance vary for 

 each antibiotic. For example, certain bacteria showed no resistance to 



