196 NATURE OF ANTIBIOTIC ACTION 



MECHANISM OF ANTIBIOTIC ACTION 



In an attempt to interpret the antibacterial activities of antibiotic 

 substances, one may benefit from a comparison of the action of these 

 substances and that of other antibacterial agents. Recent studies of the 

 mechanism of antibacterial action of chemotherapeutic agents led to 

 rather definite concepts concerning the nature of this action. The action 

 was believed to consist in depriving the bacteria of the use of enzymes 

 or metabolites by various types of interference (254). The nutritional 

 requirements of the organisms thus inhibited are more exacting than in 

 their normal state, E. coll and S. hemolyticus, when inhibited by acrifla- 

 vine components, were found to require for further growth two types 

 of material not normally added, one of which could best be replaced by 

 nucleotides, and the other by a concentrate of amino acids, especially 

 phenylalanine (557, 559). 



On the basis of the information now available, the following mecha- 

 nisms may be tentatively presented here: 



The antibiotic substance interferes with bacterial cell division, thus pre- 

 venting further growth of the organism. The cell, unable to divide, 

 gradually dies. It has been shown (359), by the use of the mano- 

 metric method, that certain bactericidal agents in bacteriostatic con- 

 centrations have no effect on the metabolic rates of bacteria, though 

 they do inhibit cell multiplication. 



The antibiotic substance interferes with the metabolic processes of the mi- 

 crobial cells, by substituting for one of the essential nutrients. It has 

 been suggested (290a) that the antibiotic effect of certain polypep- 

 tides, such as gramicidin, may be due to the presence of a ^-amino 

 acid isomer of a natural amino acid, /-leucine, required for bacterial 

 growth. 



The antibiotic substance may interfere with the vitamin utilization of the 

 organism. The staling effect of a medium, frequently spoken of in 

 connection with protozoa as "biological conditioning" of the organ- 

 ism, may serve as an illustration. Such effects have been overcome 

 by the addition of a mixture of thiamine, riboflavin, and nicotin- 

 amide (373). 



The antibiotic agent brings about the oxidation of a metabolic substance 



