224 NATURE OF ANTIBIOTIC ACTION 



flavine 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 (598, 599). 



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 (363), 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 interferes with the metabolic processes of the microbial cells 

 by substituting for one of the essential nutrients. A specific inhibitory 

 effect may be exerted by those substances that are structurally re- 

 lated to normal cell metabolites; such substances are taken up by the 

 cell in competition with normal nutrients but since they are useless to 

 the cell for further reactions they block the process of growth (253, 

 596-600). The antibiotic effect of certain polypeptides, such as 

 gramicidin, may be due to the presence of a (^-amino-acid isomer of 

 a natural amino acid, /-leucine, required for bacterial growth (289). 



The antibiotic, such as aspergillic acid, interferes with the utilization of 

 iron or with the functioning of the iron-containing enzyme system 

 (348). 



The antibiotic may interfere with the production and utilization of an es- 

 sential growth-factor required by the cell. The staling effect of a 

 medium, frequently spoken of in connection with protozoa as "bio- 

 logical conditioning" of the organism, may serve as an illustration. 

 Such effects have been overcome by the addition of a mixture of 

 thiamine, riboflavin, and nicotinamide (374). 



The antibiotic agent brings about the oxidation of a metabolic substance 

 which must be reduced in the process of bacterial nutrition, or other- 

 wise modifies the intermediary metabolism of the bacterial cell. 



The agent combines with the substrate or with one of its constituents, 

 which is thereby rendered inactive for bacterial utilization. 



The agent competes for an enzyme needed by the bacteria to carry out an 

 essential metabolic process. 



