Tetracyclines protein synthesis effects

It has been known for some time that tetracyclines are accumulated by bacteria and prevent bacterial protein synthesis (Fig. 4). Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect (85). Inhibition of protein synthesis results primarily from dismption of codon-anticodon interaction between tRNA and mRNA so that binding of aminoacyl-tRNA to the ribosomal acceptor (A) site is prevented (85). The precise mechanism is not understood. However, inhibition is likely to result from interaction of the tetracyclines with the 30S ribosomal subunit because these antibiotics are known to bind strongly to a single site on the 30S subunit (85). 

Pharmacology The tetracyclines are bacteriostatic. They exert their antimicrobial effect by inhibition of protein synthesis. Tetracyclines are active against a wide range of gram-positive and gram-negative organisms. 

Infections by the ulcer-causing bacterium Helicobacter pylori can be treated effectively with a prolonged course of doxycycline or another of the tetracycline family of antibiotics, potent inhibitors of prokaryotic protein synthesis. 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

With the exception of doxycycline and minocycline, tetracyclines inhibit to some extend protein synthesis from amino acids also in mammalian cells. This antianabolic effect is reflected by raised blood urea levels in the patient. 

Mechanism of Action A tetracycline antibacterial that inhibits bacterial protein synthesis by binding to ribosomal receptor sites also inhibits ADH-induced water reabsorption. Therapeutic Effect Bacteriostatic also produces water diuresis. Pharmacokinetics Food and dairy products interfere with absorption. Protein binding 41 %-91%. Metabolized in liver. Excreted in urine. Removed by hemodialysis. Half-life 10-15 hr. 

Mechanism of Action A tetracycline antibacterial that inhibits bacterial protein synthesis by binding to ribosomes. Therapeutic Effect Bacteriostatic. 

The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by the inhibition of protein synthesis. The tetracyclines, including doxycycline, have a similar... 

It has been known for some time that tetracyclines arc accumulated by bacteria and prevent bacterial prutein synthesis. Furthermore, inhibition of protein synthesis is responsible for the bacteriostatic effect. Inhibition... 

Tetracycline and tetracycline derivatives (see Table 33-3) inhibit protein synthesis by binding to several components of the ribosomal apparatus in susceptible bacteria.3,12 Hence, these drugs may cause misreading of the mRNA code, as well as impair the formation of peptide bonds at the bacterial ribosome. Thus, tetracyclines are very effective in preventing bacterial protein synthesis. 

The tetracyclines were discovered towards the end of the 1940 s (structure of oxytetracycline shown in Figure 5), They have a broader spectrum of activity than the early penicillins. In addition effects on bacteria are different. The penicillins are bactericidal whereas the tetracyclines are bacteriostatic, reflecting differing modes of action. Tetracyclines disrupt protein synthesis by binding to the bacterial ribosome whilst the P-lactams inhibit bacterial cell wall biosynthesis. During the 60 s, 70 s and early 80 s, tetracycline-based products made the biggest commercial impact in the animal health industry. 

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. 

Early explanations of the mechanism of action of tetracyclines involved their demonstrated ability to inhibit various bacterial enzymes that catalyzed such biochemically essential reactions as glucose oxidation and oxidative phosphorylations. Their ability effectively to chelate di- and trivalent metallic ions was also invoked in the theorization. However, at clinically achievable serum levels the bacteriostatic effects of tetracyclines are now accepted to involve primarily direct inhibition of protein synthesis. 

Protein synthesis inhibition results from reversible binding of the tetracycline drugs to the 30S ribosomal subunit. This in turn prevents the attachment of aminoacyl-fRNAs to the acceptor site of the ribosomal structure (Fig. 6-17). The ribosomal mRNA complex is thus effectively precluded from initiating protein synthesis. Tetracyclines do not interfere with actual peptide bond formation, nor with the translocation process. In vitro studies with 70S ribosomes using photoaffinity techniques demonstrate binding to the 4S and 18S protein components of the 30S subunits. It is likely that these are the actual binding sites. 

Selective toxicity of these protein synthesis inhibitors against microorganisms may be explained by target differences. Chloramphenicol does not bind to the SOS ribosomal RNA of mammalian cells, though it can inhibit the functions of mitochotidrial ribosomes, which contain 70S ribosomal RNA. Tetracyclines have little effect on mammalian protein synthesis because an active efflux mechanism prevents their intracellular accumulation. 

Tetracycline antibiotic protein synthesis inhibitor (SOS), more effective than other tetracyclines against chlamydia and in Lyme disease. Unlike other tetracyclines, it is eliminated mainly in the feces. Tox see tetracycline. 

Tetracyclines This very successful class of antibacterials act selectively on the bacterial ribosome inhibiting protein synthesis. They do not bind with mammalian ribosomes in the cytoplasm and, therefore, do not have a direct effect on the patient s metabolism. Like any drug, they are not free of potentially harmful side effects. They complex calcium and can interfere with development of the permanent teeth prior to their erupting through the gums As with the sulfonamides, this class... 

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