200 NATURE OF ANTIBIOTIC ACTION 



place before any morphological changes are observed in the cells, 

 lysis was believed to be a secondary process, following cell injury; 

 hydrolytic enzymes, however, remained unaffected. 

 5. Protection of animals by the antibiotic substance against infection. 



Tyrothricin is made up of two compounds, gramicidin and tyroci- 

 dine, that differ in their chemical properties and in their biological ac- 

 tivity (205). Gramicidin acts only against gram-positive bacteria, in- 

 cluding pneumococci, streptococci, staphylococci, diphtheria bacteria, 

 and aerobic spore-forming bacilli j meningococci and gonococci are not 

 readily acted upon. Tyrocidine affects both gram-positive and gram- 

 negative organisms. Gramicidin causes hemolysis of washed red cells, 

 this hemolytic action being destroyed on heating. Tyrocidine causes 

 lysis of many bacterial species. This action, however, is secondary, 

 autolysis following the death of the cells. Peptones and serum inhibit 

 the action of tyrocidine, but gramicidin is affected only to a limited ex- 

 tent by these agents (391, 579). 



Tyrocidine behaves as a general protoplasmic poison. The effect of 

 gramicidin, on the other hand, is reversible. Staphylococci "killed" 

 with gramicidin and no longer able to grow on organic media can be 

 made to grow in the presence of certain tissue components. Gramicidin 

 is, therefore, not considered as a gross protoplasmic poison, but retains 

 a good deal of its activity in animal tissues. When applied locally at the 

 site of the infected area, gramicidin exhibits definite action against in- 

 fection with pneumococci and streptococci. When injected intrave- 

 nously, however, it is almost completely inactive against systemic in- 

 fection. 



It was demonstrated by tissue culture technique (401) that the he- 

 molytic effect of tyrothricin was due to the presence of gramicidin. 

 When tyrothricin or gramicidin was heated in an aqueous suspension 

 there was a loss of hemolytic and bactericidal activity. Tyrocidine, 

 which is not very hemolytic, showed no marked toxic effect upon the 

 leucocytic elements of the human blood in amounts up to 100 mg. per 

 milliliter for 8 hours. 



Other investigators (728) have reported that the hemolytic activity 

 of tyrothricin is inherent rather in the tyrocidine fraction, although 

 gramicidin also exhibits a definite hemolytic action. The addition of 



