Aureomycin action

Tetracycline 4.46) and its derivatives are the most used of all broad-spectrum antibiotics . Their selectivity depends on their preferential accumulation by bacteria, as was outlined in Section 3.0. Chelation of magnesium also plays an important part in their action, and this is discussed in Section 11.8. Tetracycline was prepared by the dechlorination of its 7-chloro-derivative ( Aureomycin ), the first medicinal tetracycline, isolated in 1947 from Streptomyces aureofadens. It is a dimethylaminopentahydroxydioxo-octahydromi/>/Aac carboxamide. 

For net protein synthesis to occur in the animal body, it is necessary for the essential amino acids to be administered simultaneously for net protein synthesis to occur in suspensions of Staph, aureus, a complete amino acid mixture is required in the suspension medium, Gale and Folkes observed, however, that C Mabeled glutamic acid and phenylalanine were actively incorporated into the protein of Staph, aureus when other amino acids were absent and no increase in protein occurred. These authors point out that the inhibition of protein synthesis should affect the incorporation of all amino acids to the same extent. Actually it was observed that p-chlorophenylalanine inhibited protein synthesis and the incorporation of phenylalanine almost completely without significantly reducing the incorporation of glutamic acid. The inhibition by p-chloro-phenylalanine was strictly competitive. Study of the action of antibiotics, which also inhibit protein synthesis, revealed that the incorporation of phenylalanine was more sensitive to inhibition by chloramphenicol and aureomycin than was glutamic acid, whereas the converse was true... 

The experiments of Dixon and Thayer indicate that intramuscular injections of aureomycin and procaine penicillin G are effective in enhancing growth, possibly by gaining access to the bowel, and that functional caeca are not essential for the growth-promoting action in the bird. 

In the introduction the idea was put forward that antibiotics could be used as tools to assist in the elucidation of anabolic reactions. As each stage in amino acid assimilation has been uncovered in the course of these studies, the action of a number of antibiotics has been tested on that stage. The antibiotics used have been tyrocidin, penicillin, aureomycin, chloramphenicol (chloromycetin), terramycin, neomycin, streptomycin, bacitracin, and polymjrxin. With the exceptions of streptomycin and polymyxin, significant inhibitions of some stage or other in amino acid assimilation have been observed for all these antibiotics. These points of interference are summarized in Table XVI. 

The extracellular accumulation of peptides containing glutamic acid which occurs when Staph, aureus is incubated with glucose, glutamic acid, and either cysteine or alanine is not easily followed on an accurate quantitative basis. The action of chloramphenicol and aureomycin on the formation of these peptides has been studied and, although no clear-cut results have been obtained, it is certain that the formation is not as sensitive as protein formation is to these antibiotics. Chloramphenicol at 100 Mg./ml. is without significant effect on the formation of these peptides, while aureomycin produces a significant inhibition at 100 Mg-/ml. but not at 1 ng./ml. 

Fia. 27. Inhibitory actions of aureomycin on stages of assimilation of amino acids in Staph, aureus. Key as for Fig. 25. (Gale and Folkes, 1953b,c.)... 

The inhibitory actions of aureomycin are more complex than are those of chloramphenicol, presumably since the former acts as an uncoupling... 

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