MECHANISM OF ANTIBIOTIC ACTION 197 



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. 



The agent interferes with various enzymatic systems, such as the respira- 

 tory mechanism of the bacterial cell, especially the hydrogenase sys- 

 tem (435) and the phosphate uptake by the bacteria accompanying 

 glucose oxidation, as in the action of gramicidin. Penicillin, for ex- 

 ample, was shown (892) to be capable of inhibiting the activity of 

 urease. It was later proved (8ioa), however, that this was due not 

 to the penicillin itself but to certain impurities in crude penicillin 

 preparations. 



The antibiotic substance may inhibit directly cellular oxidations, particu- 

 larly those involving nitrogenous compounds, an action similar to 

 that of propamidine (494). 



The antibiotic substance acts as an enzyme system and produces, in the 

 medium, oxidation products, such as peroxides, injurious to the bac- 

 terial cell. The glucose oxidase produced by P. notatum (153, 492, 

 751, 902) catalyzes the following reaction: 



Glucose -j- Oo — ^ Gluconic acid -f- H2O2. 

 Xanthine oxidase acts in a similar manner (531, 79l)- 



The antibiotic substance favors certain lytic mechanisms in the cell, 

 whereby the latter is destroyed; this mechanism may be either sec- 

 ondary or primary in nature. 



The antibiotic substance affects the surface tension of the bacteria, acting 

 as a detergent; tyrocidine lowers the surface tension of the bacterial 

 cell, thereby causing its death, possibly by forming a stable complex 

 with it (189). 



The antibiotic substance may interfere with the sulfhydryl group which is 

 essential for cell multiplication. This was shown (254a) to hold true 

 for mercurials and other chemical antiseptics. The possible inter- 

 relationship between the sulfhydryl group and true antibiotics has re- 

 cently been indicated (109a). 



On the other hand, bacteria subjected to the action of an antibiotic 

 substance may develop mechanisms that render them resistant to the 



