Antibiotics bacterial protein synthesis affected

Typical classes and examples within these categories as they apply to what is currently most prescribed on the U.S. market are summarized in Table 1.8. The targets in groups 1 and 4 are unique in bacteria and absent in humans and other animals, whereas groups 2, 3, and 5 have human counterparts that are structurally different between prokaryotes and eukaryotes. These differences in targets make the use of antibiotics selective for bacteria with little or no effect on eukaryotic cells from a therapeutic perspective. However, that does not mean that antimicrobial compounds are completely inert to eukaryotes. The mechanisms that block bacterial protein synthesis, block DNA replication, and those that disrupt membrane integrity affect membrane pores. 

Protein synthesis is a central function in cellular physiology and is the primary target of many naturally occurring antibiotics and toxins. Except as noted, these antibiotics inhibit protein synthesis in bacteria. The differences between bacterial and eukaryotic protein synthesis, though in some cases subtle, are sufficient that most of the compounds discussed below are relatively harmless to eukaryotic cells. Natural selection has favored the evolution of compounds that exploit minor differences in order to affect bacterial systems selectively, such that these biochemical weapons are synthesized by some microorganisms and are extremely toxic to others. Because nearly every step in protein synthesis can be specifically inhibited by one antibiotic or another, antibiotics have become valuable tools in the study of protein biosynthesis. 

Sparsomycin, a sulfur-containing antibiotic, inhibits protein synthesis in mammalian and bacterial cells. Tryptophan administration before or after sparsomycin did not affect the hepatic polyribosomal disaggregation or the decreased protein synthesis due to sparsomycin.188 A possible explanation for the lack of effect by tryptophan may be due to sparsomycin s ability to cause fall-off ribosomes, which are defective as indicated by the decreased formation of polyphenylalanine when assayed in vitro with poly(U).207... 

It is now 25 years since specific inhibition of protein synthesis by antimicrobial agents was first reported. Specific inhibitory effects on bacterial protein synthesis by chloramphenicol and chlortetracycline, at their minimal growth inhibitory concentrations, were first described by Gale and Paine. - At those concentrations the antibiotics did not affect respiration, fermentation and amino acid accumulation but caused an immediate cessation of protein synthesis and an increase in the rate of nucleic acid accumulation in bacteria. ... 

Of the fonr possible optical isomers of chloramphenicol, only the o-threo form is active. This antibiotic selectively inhibits protein synthesis in bacterial ribosomes by binding to the 50S subunit in the region of the A site involving the 23 S rRNA. The normal binding of the aminoacyl-tRNA in the A site is affected by chloramphenicol in such a... 

To establish whether rifaximin, like the other members of the rifamycin family [36, 58], specifically inhibits bacterial RNA synthesis the effect of this antibiotic as well as that of rifampicin and chloramphenicol on RNA (via 3H-uridine incorporation), DNA (via 3H-thymidine incorporation) and protein (via 35S-methionine incorporation) synthesis was studied in growing cultures of Escherichia coli [59], While chloramphenicol reduced protein synthesis, both rifaximin and rifampicin inhibited RNA synthesis in a concentration-dependent fashion. In contrast, none of them affected 3H-thymidine incorporation into DNA. These data suggest that rifaximin, like rifampicin, inhibits RNA synthesis by binding the (3 subunit of the bacterial DNA-dependent RNA polymerase [60],... 

D. Treatment of bacterial infections Antibiotics that selectively affect bacterial function and have minimal side effects in humans are usually selected to treat bacterial infections. Rifampicin, which inhibits the initiation of prokaryotic RNA synthesis, is used to treat tuberculosis. Streptomycin, tetracycline, chloramphenicol, and erythromycin inhibit protein synthesis on prokaiyotic ribosomes and are used for many infections. Chloramphenicol affects mitochondrial ribosomes and must be used with caution. 

The selectivity of the tetracyclines, so much used in treating bacterial infections in mammals, depends on a similarly favourable distribution the bacteria concentrate these antibiotics whereas mammalian cells do not. Concentration of tetracyclines by bacteria (both Gram-positive and -negative types) was found to be a function of the cytoplasmic membrane (Franklin, 1971). Because of this difference, tetracyclines inhibit ribosomal protein synthesis in bacteria at doses which do not affect it in higher organisms (Franklin, 1963b, 1966). This selectivity depends on the intactness of the mammalian cell membrane, because isolated ribosomes (rat liver was used) were found to be as subject to inhibition of protein synthesis as bacterial ones were (Franklin, 1963a Section 11.8). 

Protein synthesis in mitochondria is dependent on the suppty of ATR either oxidative phosphorylation, or a steady supply of ATP must be provided. From a pharmacological standpoint, it is interesting that the incorporation of amino acids is affected by th3iroid hormone in vivo. The labelled amino acids are incorporated into an insoluble protein fraction present in the membrane and none of the soluble mitochondrial enzymes studied so far become labelled to any appreciable extent. The process of protein synthesis in mitochondria, as monitored by the incorporation of amino acids, displays some peculiar characteristics it is inhibited by a variety of other amino acids, possibly due to competitive effects among different amino acids for a common transport mechanism. Also peculiar is the sensitivity to chloramphenicol, and the insensitivity to cycloheximide, which is typical of bacterial systems, and not of microsomal systems. Then, there is the observation that actinomycin-D (a known inhibitor of the nuclear DNA-dependent RNA polymerase), inhibits protein synthesis in mitochondria after treatments have been applied which affect the permeability of the membrane, thus permitting penetration of the antibiotic. This last observation indicates synthesis of messenger RNA in mitochondria via a specific DNA-dependent RNA polymerase. Protdn synthesis in mitochondria is thus apparently dependent on the continuous synthesis of RNA this is possibly due to a peculiar lability of mitochondrial messenger RNA. 

Antibiotic resistance in bacteria is not a fixed property, and the degree of resistance detectable in the laboratory probably bears litde relationship to the resistance of the organism when growing in the intestinal tract of animals. The types of resistance that bacteria may develop to the action of antibiotics involve two distinct mechanisms mutation and inheritance. The former mechanism affects DNA sequence and results in the synthesis of a protein or macromolecule by the bacterial chromosome that differs from the original chemical entity, with the ability to interfere with the antibiotic activity. Because an antibiotic hinders a bacterium only after it has entered or crossed the cell wall and has bound to a target site, resistance can develop directly if the mutation has so altered the characteristics of the protein or macromolecule that the cell wall, receptor site, or transport mechanism is no longer friendly to the antibiotic. 

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