202 NATURE OF ANTIBIOTIC ACTION 



as well as actinomycin and clavacin, inhibited the coagulation of rabbit 

 plasma by staphylococci but did not prevent coagulation by sterile cul- 

 ture filtrates of these organisms j none of these three substances de- 

 stroyed the toxin, nor did they enhance its hemolytic or lethal action 



(64). 



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 in one patient (720). Various other observations have been made 

 (686) that staphylococci grown in the presence of increasing concentra- 

 tions of gramicidin become resistant to inhibition by this substance 

 (84,689). 



Both gramicidin and tyrocidine are said (196) 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 j it destroys immediately and irreversibly their meta- 

 bolic activity, such as oxygen uptake and acid production. For most 

 tissue cells, with the exception of spermatozoa, gramicidin is much 

 less toxic than tyrocidine. It behaves like a specific inhibitor of certain 

 metabolic reactions. It retains much of its activity in vivo. 



It remains to be determined to what extent the action of tyrocidine, 

 as well as of other antibiotic substances, can be reversed by detoxication 

 with high molecular anions in a manner similar to their action upon sur- 

 face active cations. The bacteria were said (901) to function as cationic 

 exchanges, both the surface and the adsorbability depending on the 

 structure of the cation. The bacterial action of surface-active cations and 

 of toxic metallic ions and dye cations was considered as a phenomenon 

 of ionic exchange by bacteria. Harmless cations could thus exert a pro- 

 tective action on bacteria against the toxic cations. 



Penicillin 



Although penicillin is active primarily on gram-positive bacteria, it 

 also has an effect on certain gram-negative bacteria, but not on the colon 

 organism, Hemofhilus, or Brucella. The gram-negative cocci can be 



