206 NATURE OF ANTIBIOTIC ACTION 



hydrolyzate medium j the activity was increased to 6,000 by addition 

 of /)-amino-benzoic acid in dilution of 1 12,500 to i : 10,000 j this was 

 also true in presence of glucose in test medium. A similar, although 

 somewhat lower, increase took place in case of S. aureus; no effect was 

 obtained on S. hemolytkus. The addition of a dilute solution of sulfa- 

 pyridine, which in itself had little inhibiting effect, exerted an even 

 greater synergistic action upon penicillin. This effect was exerted not 

 only in vitro but also in vivo (896). 



Attention was directed previously to the production by P. notatum 

 of an oxidative enzyme. It is interesting to find that P. chrysogenum 

 also forms an oxytropic glucose-dehydrogenase that is not susceptible to 

 CO and cyanide (523) ; the glucose is oxidized to gluconic acid. The 

 active substances produced by both groups are thus similar (832). 



Other Antibiotic Agents 



Of the other agents, actinomycin, streptothricin, clavacin, gliotoxin, 

 and several other mold products deserve particular attention. 



Actinomycin is a bacteriostatic agent, active primarily against gram- 

 positive bacteria. It is extremely toxic to animals, a factor which limits 

 its practical utilization. One milligram of actinomycin given to mice, 

 rats, or rabbits intravenously, intraperitoneally, subcutaneously, or 

 orally proved (757) to be lethal for i kilogram weight of the animals. 

 Doses as small as 50 y per kilogram injected intraperitoneally daily for 

 6 days caused death accompanied by severe gross pathological changes, 

 notably a marked shrinkage of the spleen. Actinomycin is rapidly re- 

 moved from the blood and excreted. It has no effect upon bacteriophage 

 or staphylococci, although o.i milligram per cent inhibits growth as 

 well as blood coagulation by these organisms {6'^';})). 



A comparison of the effect of actinomycin with that of tyrothricin 

 and its constituents, tyrocidine and gramicidin, upon the growth of 

 rhizobia (890) showed that, whereas gramicidin inhibited all strains 

 alike, the other three substances inhibited the slow-growing rhizobia 

 much more than the fast-growing ones. Effective and ineffective strains 

 behaved alike. Of the four antibiotic substances, tyrocidine was usually 

 bactericidal, actinomycin was bacteriostatic, and the other two pos- 



