MODES OF ACTION OF ANTIBIOTICS 



91 



the hydrogenase system and the phosphate 

 uptake by the bacteria accompanying glu- 

 cose oxidation. 



4. The antibiotic inhibits celhilar oxida- 

 tions involving nitrogenous compounds. 



5. The antibiotic interferes with the pro- 

 duction and utilization of a growth factor 

 essential to the cell. 



6. The antibiotic combines with the sub- 

 strate or with one of its constituents, which 

 is thereby rendered inactive for liacterial 

 utilization. 



7. The antibiotic favors certain lytic 

 mechanisms in the cell, resulting in destruc- 

 tion of the cell. 



8. The antibiotic affects the surface ten- 

 sion of the sensitive organisms, acting as a 

 detergent. 



9. It has also been suggested that the 

 activity and specificity of an antibiotic are 

 functions of several factors, such as ditfusi- 

 bility of the antibiotic into the microl;)ial 

 cell, adsorption by various enzyme systems, 

 its reaction with sulfhychyl groups of the 

 enzymes or with other sulfhydryl-containing 

 substances adsorbed by the enzymes. 



10. The concentration of the antibiotic 

 and the composition of the mediiun ai'e 

 highly important in modifying the activity 

 of the antibiotic. Some antibiotics lose con- 

 siderable bacteriostatic activity when incu- 

 bated with sterile l)roth. 



The majority of antibiotics exert not only 

 a marked bacteriostatic effect, but also a bac- 

 tericidal action. This effect is accelerated by 

 an increase in temperature from 4 to 42°C, 

 but is impaired by an increase in acidity of 

 medium between pH 7.0 and o.O. The rajiid 

 drop in the number of bacteria within the 

 first 15 minutes after the application of 

 penicillin was interpreted as indicative of its 

 bactericidal action. Young cells are particu- 

 larly susceptible, whereas mature cells are 

 neither lysed nor readily killed. The bacterio- 

 lytic action of penicillin upon sensitive or- 



ganisms is greatest at the maximal rate of 

 multiplication. 



Host defenses play a significant role in the 

 clinical efficacy of antibiotics. Here too, 

 however, the precise mechanisms still await 

 clarification. It has been reported, for ex- 

 ample, that prior treatment of bacteria with 

 penicillin or with streptomycin sensitizes the 

 organisms to phagocytosis (Linz, 1953). The 

 fact that chlortetracycline, oxytetracycline, 

 and chloramphenicol are therapeutically 

 effective at bacteriostatic rather than bac- 

 tericidal concentrations implicates the host 

 defense mechanisms in clinical medicine. 

 These observations were sunmiarized by 

 Eagle and Saz (1955). 



Chain and Florey (1944) divided all the 

 antibiotics into two groups: (1) those that 

 react with the protoplasm of the cell, thus 

 killing l)otli microbial and animal cells, 

 comparable to the action of chemical anti- 

 septics; and (2) those that I'eact with sul)- 

 stances ha^•ing a specific significance in the 

 growth of the bacterial cell. Some of the anti- 

 })iotics were found to be largely growth in- 

 hibiting and have therefore been designated 

 as "bacteriostatics." With the broadening 

 knowledge of antibiotics, this classification 

 became too limited in scope. 



It has also been suggested that the chemo- 

 therapeutic potentialities of antibiotics may 

 be measured by their effects on bacterial 

 respiration. If the latter is stopped by the 

 addition of an antibiotic in dilution of 1: 

 1000, the organisms may be said to have 

 been killed; such an antibiotic would there- 

 fore be toxic to animal tissues. If, however, 

 the antibiotic produces little or no effect on 

 the respii'ation of bacteria, the probability 

 was suggested that the antibiotic might pos- 

 sess chemotherapeutic possibilities. 



The antibiotics produced by actinomy- 

 cetes were shown to affect the growth of 

 certain bacteria, such as B. inycoides, in the 

 following manner: Cell division is delayed; 

 the cells become elongated, reaching enor- 



