ANTIBACTERIAL ACTION 201 



glucose caused only slight inhibition of the hemolytic effect. Gramicidin 

 was found to be effective, in amounts as low as i mg., upon a billion 

 gram-positive organisms, whereas tyrocidine acted in 25 to 50 times that 

 concentration in the absence of inhibitors (435, 436). Tyrocidine ap- 

 peared to block all the oxidative systems of the bacteria studied, whereas 

 gramicidin seemed to affect only certain individual reactions. Both sub- 

 stances were found to exert a protective antibacterial action in mice in- 

 fected intraperitoneally with susceptible bacteria 5 gramicidin protected 

 the animals at a level one-fiftieth as high as that required for tyrocidine. 

 Both substances are toxic to animals when injected into the blood 

 stream J both are leucocytolyticj they show little toxicity when applied 

 locally by the subcutaneous, the intramuscular, or the intrapleural 

 route J oral administration is not accompanied by toxic effects, but such 

 treatment is ineffective (729). 



Gramicidin remains active in the blood stream, but it has only weak 

 bacteriostatic properties and no bactericidal action. Tyrocidine is 

 strongly bactericidal but it is inactivated by blood serum, hence it is 

 limited to local applications. No specific effect was exerted by these sub- 

 stances on respiratory or circulatory systems (756). 



According to Dubos (189, 201), the retention of the stain by gram- 

 positive bacteria indicates a peculiar property of the cell wall of these 

 organisms. The addition of 0.00 1 mg. of gramicidin to a billion pneu- 

 mococci, streptococci, staphylococci, and others is considered sufficient 

 to inhibit the growth of these organisms on subsequent transfers. This 

 effect was said to be due not to an alteration of the protoplasm but to 

 some specific interference with an essential metabolic function. Bacterial 

 cells which have become inhibited under the action of gramicidin be- 

 come viable again when cephalin is added to the medium. It was sug- 

 gested that the ineffectiveness of gramicidin on gram-negative bacteria 

 may be due to the presence of a phospholipid in these organisms. 



Tyrothricin did not exert any effect upon staphylococcus bacterio- 

 phage (633). It did, however, inhibit the fibrinolytic activity of heta- 

 hemolytic streptococci as well as of the supernatant liquids of these bac- 

 teria but not of partially purified fibrinolysin. Although it prevented 

 the neutralization of hemotoxin by antitoxin, it did not inhibit the pro- 

 tective action of antitoxin against the toxin in mice (64). This substance, 



