128 FUNGI AS ANTAGONISTS 



bacteria belonging to the colon-typhoid-dysentery group were not af- 

 fected. The culture filtrate of the fungus was found to contain an active 

 substance, which was designated as penicillin. 



A glucose-nitrate solution was used as the basic medium for the pro- 

 duction of penicillin. It was supplemented with yeast-extract or corn 

 steep liquor, or brown sugar was employed in place of glucose j the 

 growth of the organism and the production of the antibacterial sub- 

 stances were thus greatly facilitated (7, 282, 804). The reaction of the 

 medium was found to change from slight acidity initially (^H 6 to 7) 

 to distinct acidity (^H 3.0), followed later by alkalinity, finally reach- 

 ing a /)H of 8.0 or even 8.8. A faint to deep yellow color is produced in 

 the medium. Penicillin production is usually at its maximum at about 

 -pH. 7 and may remain constant for several days or may fall again rap- 

 idly. Aerobic conditions are essential for the formation of penicillin. 

 Once a fungus pellicle has been produced, the medium can be replaced 

 several times, giving fresh lots of penicillin in about half the time re- 

 quired during the initial growth period. Crude penicillin cultures are 

 capable of inhibiting the growth of staphylococci in dilutions of i : 800 j 

 recently, even more active preparations were obtained. 



There is considerable variation in sensitivity to penicillin among bac- 

 teria belonging to the same group : 27 strains of enterococci and 6 strains 

 of S. lactis were shown to be resistant to the action of this agent, whereas 

 13 strains of S. viridans were susceptible (79). The ability of a strain 

 to resist the action of penicillin can be greatly increased by successive 

 transfers of the culture to media containing this substance (564, S^^)-' 



Chain et al. (113) were the first to succeed in isolating from the cul- 

 ture medium of P. notatum a water-soluble, stable, brown powder 

 which had marked antibacterial activity. This preparation inhibited, in 

 dilutions of i to several hundred thousand, the growth of many aerobic 

 and anaerobic bacteria. The active material was relatively nontoxic to 

 laboratory animals. Intravenous and subcutaneous injections of 10 mg. 

 or more to mice had little or no effect. The material was active m vivo, 

 subcutaneous injections saving the lives of mice injected intraperitone- 

 ally with S. pyogenes or S. aureus. Intramuscular infections of mice 

 with CI. sefticum were also successfully treated by repeated subcutane- 

 ous injections of penicillin. 



