Streptomycin, protein synthesis

Inside the cell, aminoglycosides bind to specific 30S-subunit ribosomal proteins (S12 in the case of streptomycin). Protein synthesis is inhibited by aminoglycosides in at least three ways (Figure 45-3) (1) interference with the initiation complex of peptide formation (2) misreading of mRNA, which causes incorporation of incorrect amino acids into the peptide and results in a nonfunctional or toxic protein and (3) breakup of polysomes into nonfunctional monosomes. These activities occur more or less simultaneously, and the overall effect is irreversible and lethal for the cell. 

Streptomycin Protein synthesis inhibition Deafness, vestibular dysfunction, nephrotoxicity... 

Streptomycin Protein synthesis inhibition see Aminoglycoside, pages 187-188) Deafness Vestibular dysfunction Nephrotoxicity... 

Streptomycin Streptomyces griseus Gram-negative bacteria Protein synthesis... 

Chloroplast protein synthesis is controlled largely at the post-transcriptional level [20,21] and can be repressed by the inclusion of antibiotics such as streptomycin in the sprouting medium. Streptomycin binds to the 16S rRNA and causes the ribosome to misread the mRNA sequence, producing incorrect and non-functional proteins [22]. 

Other key classes of antibacterials include the tetracyclines (Aureomycin, Terramycin), macrolides (erythromycin, Zithromax, Biaxin), and aminoglycosides (streptomycin, amikacin, neomycin). These antibacterials are protein synthesis inhibitors. 

Pharmacology Streptomycin sulfate is a bactericidal antibiotic that interferes with normal 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). 

Streptomycin and other aminoglycosides inhibit bacterial protein synthesis by binding... 

The selection of transformed chloroplasts usually involves the use of an antibiotic resistance marker. Spectinomycin is used most routinely because of the high specificity it displays as a prokaryotic translational inhibitor as well as the relatively low side effects it exerts on plants. The bacterial aminoglycoside 3 -adenyltransferase gene (ciadA) confers resistance to both streptomycin and spectinomycin. The aadA protein catalyzes the covalent transfer of an adenosine monophosphate (AMP) residue from adenosine triphosphate (ATP) to spectinomycin, thereby converting the antibiotic into an inactive form that no longer inhibits protein synthesis for prokaryotic 70S ribosomes that are present in the chloroplast. 

All aminoglycosides act by inhibiting protein synthesis of bacteria by directly combining with ribosomes. They penetrate the outer cytoplasmic membrane and inhibit protein synthesis. Streptomycin combines with the bacterial 30S ribosomes and inteferes with the mRNA-ribosome combination. Other aminoglycosides bind to additional sites on SOS subunit as well as to 30S-50S interface. 

Streptomycin Prevents bacterial protein synthesis by binding to the S12 ribosomal subunit (see also Chapter 45) Bactericidal activity against susceptible mycobacteria Used in tuberculosis when an injectable drug is needed or desirable and in treatment of drug-resistant strains IM, IV renal clearance (half-life 2.5 h) administered daily initially, then 2 x week Toxicity Nephrotoxicity, ototoxicity... 

Compounds such as puromycin and cycloheximide, which block rRNA transfer, and streptomycin and lincomycin, which cause misreading of messenger RNA (mRNA), block protein synthesis and are therefore often embryolethal. 

The glycoside/aminoglycoside antibiotics, like the macrolides, exert a bacteriostatic effect due to selective inhibition of bacterial protein synthesis, with the exception of novobiocin (26). The compounds neomycin (27), spectinomycin (28) and streptomycin (29) bind selectively to the smaller bacterial 30S ribosomal subunit, whilst lincomycin (30) binds to the larger 50S ribosomal subunit (cf. macrolides). Apramycin (31) has ribosomal binding properties, but the exact site is uncertain (B-81MI10802). Novobiocin (26) can inhibit nucleic acid synthesis, and also complexes magnesium ion, which is essential for cell wall stability. 

Inhibition of protein synthesis Streptomycin Tetracyclines Inhibits initiation stage Inhibits binding of aminoacyl-tRNA to 30S ribosomal subunit... 

Inhibition of protein synthesis by aminoglycoside antibiotics, especially by streptomycin, is bactericidal (rev.46)). The antibiotic binds to the smaller ribosomal subunit and leads to the formation of abortive initiation complexes of ribosomes, streptomycin and amino acyl tRNA which progressively trap ribosomes in the form of such biologically irreversible complexes. When protein synthesis is prematurely terminated by puromycin and ribosomes are thus made available for reinitiation of de novo protein biosynthesis, the bactericidal action of streptomycin is accelerated47). Destruction of ribosomes under the influence of primaquine operationally also results in non-occurrence of protein synthesis and in a marked bactericidal effect48, 49 ... 

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