MECHANISM OF ANTIBIOTIC ACTION 227 



and C. difhtheriae, by preventing the utilization of pantothenic acid by 

 these bacteria, for which it is an essential metabolite. Fildes (253) em- 

 phasized that "chemotherapeutic research might reasonably be directed 

 to modification of the structure of known essential metabolites to form 

 products which can block the enzyme without exhibiting the specific 

 action of the metabolite." Since /)-amino-benzoic acid has no such action 

 on penicillin, it is assumed that its mode of action upon bacteria is dif- 

 ferent from that of sulfanilamide. However, it was suggested that 

 penicillin as well acts by inhibiting directly one or more enzymes, the 

 difference being merely one of degree (648). 



The antibacterial activity of iodinin is neutralized by quinonesj this 

 is probably due to the destruction of the iodinin, since the N-oxide is 

 reduced by the organism (596, 597, 1009). Different anti-inhibitors are 

 known for other antibiotic substances, as shown later. 



Numerous other examples of metabolite-antagonism can be cited. 

 Since the nature and function of the various metabolites are so diverse, 

 and there are so many ways of modifying their structure, the principle 

 of interference with biological processes through the use of analogs of 

 essential metabolites is considered as established (994). The interfer- 

 ence is sometimes explained as a direct competition between the metabo- 

 lite and its analog for some cellular component for which they both 

 have great affinity. However, in addition to competition, other factors 

 also operate. The majority of the interferences involve organisms that 

 are unable to synthesize the essential metabolite the function of which 

 is disturbed. 



Mcllwain recommended the use of an antibacterial index to repre- 

 sent the minimal value of Ci/Cm, or the ratio of concentration of in- 

 hibitor (Ci) just sufficient to prevent the growth of the organism, to the 

 concentration of metabolite (Cm) present. The smaller the antibacterial 

 index the more effective is the compound, therefore, as an inhibitor. 

 With S. hemolytkus, the homopantoyltaurine was found to have an 

 index of 20,000, the pantoyltauramide 2,000, and the pantoyltaurine 

 500. The indices vary for different organisms. E. coU and P. vulgaris 

 synthesize their own pantothenate and are not inhibited by these ana- 

 logs of pantothenic acid. The mechanism of the resistance is at present 

 unknown. 



