134 FUNGI AS ANTAGONISTS 



giving fresh lots of penicillin in about half the time required for the 

 initial growth. Crude penicillin cultures are capable of inhibiting the 

 growth of staphylococci in dilutions of i : 8oo. Recently, much more 

 active preparations have been obtained ( i : 1 0,000 ). 



Chain et al. (123) 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. seftkum were also successfully treated by repeated subcutane- 

 ous injections of penicillin. 



An extensive literature soon began to accumulate on the production 

 (127, 128, 171, 281), isolation, and identification of penicillin. The 

 course of its formation in the culture of the organism is illustrated in 

 Figure 13. Conditions of nutrition were found to be particularly im- 

 portant. Preparations having an activity of 2,000 Oxford units or 100,- 

 000,000 dilution units have been obtained. The importance of the dual 

 nature of P. notatum (the culture being composed of two distinct cell 

 constituents) must be recognized for maximum penicillin production 

 (34, 377). The low toxicity of penicillin, its solubility in water, and its 

 in vivo activity make it an ideal agent for combating disease caused by 

 gram-positive bacteria. 



P. notatum represents an extremely variable group of organisms, 

 some strains producing considerable penicillin, others producing little 

 penicillin but large amounts of a second factor, designated as penatin or 

 notatin. Some strains of a closely related fungus, P. chrysogenumy are 

 also capable of producing penicillin that is apparently the same as the 

 penicillin of P. notatum. The P. notatum-chrysogenum group of fungi 

 is widely distributed in nature, having been isolated from different soils 

 and from various moldy food products j however, only a few strains 

 produce enough penicillin to justify their use for the commercial pro- 

 duction of this substance. 



