MODES OF ACTION OF ANTIBIOTICS 



99 



pacity to chelate or otherwise bind the 

 functional Mn. The locus of inhibition was 

 shown to be at the level of the reoxidation of 

 reduced flavin mononucleotide. It was fur- 

 ther observed that the nitroreductase was 

 indeed a portion of the electron transport 

 system of the cell. Thus, inhibition of this 

 aspect of the metabolism of the cell could 

 conceivably account for the antibiotic prop- 

 erties of chlortetracycline. It should be noted 

 that the system described was 100-fold more 

 sensitive to chlortetracycline than to oxy- 

 tetracycline and tetracycline. It is of interest 

 that a similar system isolated from a chlor- 

 tetracycline-resistant mutant derived by 

 serial passage from the parent sensitive 

 strain was resistant to chlortetracycline. 

 The presence of firmly bound metal was 

 postulated, and thus the resistant extract 

 successfully competed with the chlortetra- 

 cycline for essential cation (Saz et al., 1956; 

 Saz and Martinez, 1958, 1960). 



Weinberg (1954) investigated the effects 

 of cations on oxytetracycline inhibition of 

 Ps. aeruginosa and other cells. The various 

 cations had profound effects on the toxicity 

 of the antibiotic for the cells. Some metals 

 were antagonistic to oxytetracycline, while 

 others potentiated the effects. Rokos ct al. 

 (1958) have shown that the inhibiting effect 

 of sodium citrate on the action of chlortetra- 

 cycline on lipase and D-amylase can be ex- 

 plained by the removal of the calcium ion 

 from the system. 



The additive effects of chloramphenicol 

 and tetracyclines were discussed l)y (iale 

 and Folkes (1953) and Ciak and Hahn 

 (1958). 



Erythromycin 



Erythromycin is active largely upon gram- 

 positive cocci and upon rickettsial organisms. 

 It is either bacteriostatic or bactericidal, 

 depending on the sensitivity of the organism 

 and concentration of the antibiotic. It is 



active upon multiplying cells but not upon 

 fully grown ones (Haight and Finland, 1952). 



Neomycin, Kanamycin, and Other Memhers 

 of the Neomycin Complex 



Gale (1952) made a comparative study 

 of the effect of neomycin and various other 

 antibiotics on amino acid assimilation by 

 Staph, aureus. The accumulation of lysine 

 and glutamic acid within the cells was not 

 affected. Protein synthesis was interfered 

 with, however, but not nucleic acid synthe- 

 sis. Ihe action of neomycin was similar, in 

 this system, to that of chloramphenicol. 



According to Tsukamura (I960), kana- 

 mycin inhil)its the incorporation of P^^ 

 into the nucleic acid and protein tractions 

 and the incorpoi'ation of S^^ into the tri- 

 chloroacetic acid-soluble and protein (tri- 

 chloroacetic acid-insoluble) fractions of the 

 parent sensitive strain of Mycohacterium 

 avium, but not of the kanamycin-resistant 

 strain. The ratio of RNA to DXA is higher 

 in the kanamycin-resistant strain than in the 

 parent sensitive strain. 



Novoljiocin 



The effect of novobiocin on the turbidity 

 and viable cells of a growing culture of E. coli 

 is shown in Fig. 7. In the case of Staph, au- 

 reus, it causes the accumulation of N-acetyl- 

 amino sugar. The fact that the L-isomer 

 exhibits a totally different kind of antibacte- 

 rial activity, showing a different antibiotic 

 spectrum and a different dose response 

 correlation, was interpreted by Hahn (1958) 

 as illustrating the problematic nature of 

 structure-activity relationship. 



Puromycin 



Puromycin was found (Creaser, 1955) to 

 be an inhibitor of induced enzyme (i3-galac- 

 tosidase) synthesis in Staph, aureus. Chemi- 

 cally, this antibiotic consists of an amino- 

 nucleoside linked to an amino acid. 



