98 



NATURE, FORMATION, AND ACTIVITIES 



Q800 

 UJ 



Z) 



z 



(J 6001- 



> 

 X400 



O 



o 



^200 

 Ld 



CHLORTETR. (10 pg) 



o • 



/ ^A ___^D DIHYDROSTREPT. (1000 /ug) 



oy/' 



/ x° 



/5/ 



/7 



nt_L 





_0— • CHLORTETRA. (10 /jg) 



PLUS DIHYDROSTREPT. 

 (lOOO^g) 



i — I 1 — i — I 1 I I I I I 



^0 2 4 6 8 10 12 



TIME IN HOURS 



Figure G. Influence of time on the effect of oxygen uptake by Br. melitensis by chlortetracy- 

 cline, dihydrostrei^tomycin, and chlortetracycline plus dihydrostreptomycin. Glucose added at zero 

 hour. (Antil)iotics in presence of cells for 1 hour at room temperature and 35 minutes at 37°C be- 

 fore addition of glucose.) Endogenous respiration values subtracted. (Reproduced from McCullough, 

 N. B. and Beal, G. A. J. Infectious Diseases 90: 196-204, 1952.) 



the formation and utilization of the particu- 

 lar constituent. 



In Staph, aureus, protein synthesis, as 

 measured by the incorporation of isotopi- 

 cally labelled glutamate, was inhibited by 

 concentrations (0.2 to 0.4 /xg per ml) of 

 chlortetracycline and oxytetracycline which 

 were lower than the growth inhibitory levels 

 (O.o to 1 .0 /ig per ml). A concentration of oO 

 to 500 iJLg per ml was refiuired for inhibition 

 of nucleic acid synthesis, free glutamate 

 incorporation, or glucose fermentation (Gale 

 and Folkes, 1958). Glutathione synthesis by 

 suspensions of Proteus was iminhibited even 

 by high concentrations of oxytetracycline 

 and chlortetracycline (Samuels, 1953). 



Chlortetracylcine in low concentrations 



inhibited the synthesis of RNA and DNA by 

 Lactobacillus casei, and folic acid and vitamin 

 Bi2 were reported to prevent this inhibition 

 (Rege and Sreenivasan, 1954). 



Reports have indicated that the tetracy- 

 clines inhibit Aarious enzymatic reactions 

 and growth of sensitive organisms by inter- 

 fering with inorganic ion metabolism. 



A highly purified nitroreductase isolated 

 from a chlortetracycline-sensitive E. coli 

 was found to be markedly sensitive to pre- 

 cisely those concentrations of the antibiotic 

 which were growth inhibitor^^ Resolution of 

 the enzyme complex indicated that the re- 

 ductase was a manganoflavoprotein and 

 that chlortetracycline inhibited the nitro- 

 reductase, presumably as a result of its ca- 



