MODES OF ACTION OF ANTIBIOTIC'S 



95 



cock (l!t()Oa) examined in detail the factors 

 invol\'ed in bactericidal action of strepto- 

 mycin upon Staph, aureus. 



The ability of streptomycin to destroy 

 chloroplasts was first demonstrated by von 

 Eiiler (1947). ProvasoU et al. (1951) have 

 shown that bleached races of the flagellate 

 Eiiglena gracilis can thus be obtained. In 

 the absence of an added energy supply, 

 streptomycin also acts as an inhibitor of 

 biosynthesis by protoplast lysates and ghosts 

 of E. coli (Reiner et al., 1958). 



The antibacterial activity of streptomycin 

 can be largely or completely neutralized or 

 antagonized by an anaerobic environment 

 and by various chemical agents. These in- 

 clude glucose and certain other sugars, cer- 

 tain sulfhydryl compounds, and ketone 

 reagents. The effect of cysteine, of cevitamic 

 acid, and of ketone reagents in inhibiting 

 streptomycin activity may l)e associated 

 with the blocking of the active grouping in 

 the molecule of streptomycin. 



Streptomychi is adsorbed on the bacterial 

 surface, resulting in a reduction of th(^ net 

 negative charge, a change which affects the 

 electrophoretic mobility of some of the cells 

 (McQuillen, 1951). The effect of streptomy- 

 cin on the intermediary carbohydrate metab- 

 olism, especial!}^ to the acetate or pyruvate 

 stage, of the bacteria and on amino acid 

 utilization has been variously postulated 

 (UiMarco, 1958). The bacterial cell tries to 

 escape the antibacterial action of the anti- 

 biotic, which was believed to be due to 

 interference with the synthesis of cell-wall 

 material, by the synthesis of a different kind 

 of cell-wall substance. Streptomycin-re- 

 sistant mutants of bacteria may show new 

 deficient characters (Kohiyama and Ikeda, 

 19G0). 



Slreptothricin 



Streptothricin and streptomycin are both 

 active against gram-posit i\'e and gram- 

 negative bacteria, ])ut they differ in their 



antibiotic spectra and in their toxicity to 

 animals, the first exerting a delayed toxic 

 action. They are soluble in water but insolu- 

 ble in alcohol and other organic solvents. 

 Both have an optimal reaction at pH 8.0, 

 and both are repressed by glucose and by 

 acid salts. They are both stable compounds 

 and are highly resistant to the action of 

 microorganisms. However, the two sub- 

 stances can be differentiated in their rela- 

 tion to cysteine. Streptomycin becomes in- 

 activated by the addition of 3 to 5 mg of this 

 compound to 100 jug of the antibiotic, 

 whereas streptothricin is not affected by 

 cysteine. Streptothricin is also active upon 

 fungi, but streptomycin is not. 



Chloramphenicol 



Chloramphenicol is structurally related to 

 p-nitrophenylserinol. Numerous attempts 

 were therefore made to re^•erse the bacterio- 

 static activity of this antibiotic by aromatic 

 amino acids. Woolley (1950) reported that 

 the growth-inhibitory activity of chloram- 

 phenicol at a concentration of 1 Mg per ml on 

 E. coli was completely reversed by the addi- 

 tion of phenylalanine to the medium at a 

 concentration of 500 ^g per ml. Xo reversal 

 of acti^'ity was obtained, however, when the 

 chloramphenicol concentration was greater 

 than 2 ^g Pf'i" n^l- Similar I'esults were ob- 

 tained with tyrosine and tryptophan. With 

 Lactobacillus casei, only phenylalanine was 

 effective in reversal and, as with E. coli, 

 reversal occurred only within a narrow range 

 of concentrations of the antibiotic. Mentzer 

 et al. (1950) reported the antagonistic ef- 

 fects of glycine upon the inhibition of E. 

 coli by chloramphenicol; aspartic acid and 

 serine also showed some antagonistic poten- 

 tialities; tryptophan was without effect. 

 Truhaut et al. (1951) reported that chlor- 

 amphenicol inhibited both synthesis and 

 breakdown of tryptophan or its precursors 

 (anthranilic acid, indol) by Salmonella ty- 

 phosa. 



