232 NATURE OF ANTIBIOTIC ACTION 



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 (793). 



According to Dubos (200), the retention of the stain by gram-posi- 

 tive bacteria indicates a peculiar property of the cell wall of these or- 

 ganisms. The addition of one microgram of gramicidin to a billion 

 pneumococci, streptococci, and staphylococci is considered sujEficient to 

 inhibit the growth of these organisms on subsequent transfers. This 

 effect v/as 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 been inhibited by the action of gramicidin become 

 viable again when cephalin is added to the medium. It was suggested 

 that the ineffectiveness of gramicidin against gram-negative bacteria 

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



Different strains of S. aureus differ in their susceptibility to the ac- 

 tion of tyrothricin. There is apparent adaptation of the organism to in- 

 creasing concentrations of the substance. A marked increase in resist- 

 ance of the infecting organism, after several weeks of therapy, was ob- 

 served (752). Staphylococci grown in the presence of increasing con- 

 centrations of gramicidin become resistant to inhibition by this sub- 

 stance (81, 720). 



Both gramicidin and tyrocidine are said (206) to be surface-active 

 compounds, their antibacterial action being inhibited by phospholipids. 

 Tyrocidine behaves like a cationic detergent j it is bactericidal in buffer 

 solutions for all bacterial species so far tested, with the exception of the 

 tubercle bacillus. Gramicidin influences some energy-using process 

 which would normally allow carbohydrate and phosphate storage. This 

 effect is specific, since penicillin and sulfanilamide do not have the same 

 effect upon the phosphate metabolism of staphylococci. On the other 

 hand, like many surface detergents, tyrocidine modifies the surface of 

 the bacterial cell in such a manner that vital soluble metabolites, such 

 as nitrogen compounds, inorganic phosphate, and phosphate esters are 

 washed out of the cell. Hotchkiss (449) concluded that although ty- 

 rothricin and its constituents are more active against gram-positive than 

 gram-negative organisms, Neisseriae respond more like gram-positive 



