230 NATURE OF ANTIBIOTIC ACTION 



1. Inhibition of growth. Certain gram-positive bacteria are inhibited by 



as little as i microgram or less of the substance per lo milliliters of 

 nutrient broth or agar, thus giving an activity of i : 10,000,000 or 

 more. 



2. Bactericidal action consists in the killing of the bacterial cells, either in 



a washed state and suspended in saline, or in a growing state in broth 

 culture. 



3. Lytic activity comprises the rate of lysis of a suspension of bacterial 



cells. Streptococci, for example, are readily lysed by gramicidin, 

 whereas staphylococci are acted upon more slowly and less com- 

 pletely. 



4. Inhibition of enzyme activity includes dehydrogenases or enzymes of 



respiration. Gram-positive cocci, incubated at 37° C, lose their abil- 

 ity to reduce methylene blue in the presence of glucose, upon addi- 

 tion of gramicidin. Since inactivation of the dehydrogenase takes 

 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. 



Gramicidin and tyrocidine differ in chemical properties and in bio- 

 logical activity. 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 (617). 



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 infection, gramicidin exhibits definite action against pneumococci 



