Chloramphenicol Staph, aureus

The sensitivity of the organisms to nitrofurantoin and five other antibiotics and chemotherapeutic agents was compared and, except for the greater sensitivity of Proteus to nalidixic acid, none of the test compounds surpassed the results achieved with nitrofurantoin. An interesting study by King proved that cultures of E. coli and Staph, aureus taken at the Cleveland Clinic in the U.S. between 1956 and 1961 showed increased sensitivity to nitrofurantoin but increased resistance to dihydrostreptomycin, chloramphenicol and neomycin. 

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 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. 

Fig. 26. Progress curves for (a) nucleic acid synthesis and (b) protein synthesis in washed suspensions of Staph, aureus incubated with 1, glucose and a complete mixture of amino acids 2, as (1) - - complete mixture of purines and pyrimidines 3, as (2) + 30 Mg. chloramphenicol/ml. 4, glucose and mixture of purines and pyrimidines 5, as (4) -t- 30 Mg. chloramphenicol/ml. (Gale and Folkes, 1953b.)...

Fig. 30. Effect of chloramphenicol on the rate of incorporation of C Mabeled glutamic acid into the protein of Staph, aureus when the cells are incubated with glucose and (1) glutamic acid only or (2) a complete mixture of amino acids, including glutamic acid. (Gale and Folkes, 1953,c.)...

A question which any speculation about the template theory must take into account is What is the form of the amino acid residue which enters into combination with the template and gives rise to the protein It could be postulated that amino acids themselves are protein precursors, or that small peptides are formed first and that these combine at the template surface. The former postulate would allow for complete randomization of the amino acid residues. It is relevant in this connection to note that neither the formation of extracellular peptides by Staph, aureus (Table XVI) nor the synthesis of glutathione by cell-free extracts of Esch. colt (Samuels, 1953) is sensitive to chloramphenicol, etc., and so the formation of simple peptides cannot be taken as a model of protein syn-... 

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