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Antibiotics; Inhibitors of Protein and DNA Synthesis

LECTURE 23:. Antibiotics; Inhibitors of Protein and DNA Synthesis. Microbiology and Virology; 3 Credit hours Atta- ur - Rahman School of Applied Biosciences (ASAB) National University of Sciences and Technology (NUST). Inhibitors of Protein Synthesis. They are mostly bacteriostatic .

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Antibiotics; Inhibitors of Protein and DNA Synthesis

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  1. LECTURE 23: Antibiotics; Inhibitors of Protein and DNA Synthesis Microbiology and Virology; 3 Credit hours Atta-ur-Rahman School of Applied Biosciences (ASAB) National University of Sciences and Technology (NUST)

  2. Inhibitors of Protein Synthesis • They are mostly bacteriostatic. • Antimicrobials that bind to the 30s Ribosomal Subunit • Antimicrobials that bind to the 50s Ribosomal Subunit • Antimicrobials that interfere with Elongation Factors • The selectivity of these agents is a result of differences in the prokaryotic 70S ribosome and the 80S eukaryotic ribosome. • Since mitochondrial ribosomes are similar to prokaryotic ribosomes, these anti-metabolites can have some toxicity.

  3. 1- Aminoglycosides • The aminoglycosides (streptomycin, neomycin, netilmicin, tobramycin, gentamicin, amikacin, etc.)bind irreversibly to the 16S rRNA in the 30S subunit of bacterial ribosomes. • It has been proposed that some aminoglycosides prevent the transfer of the peptidyltRNA from the A-site to the P-site, thus preventing the elongation of the polypeptide chain. Aminoglycosides Interfering with the Translocation of tRNA from the A-site to the P-site

  4. 2- Tetracycline • Thetetracyclines (tetracycline, doxycycline, demeclocycline, minocycline, etc.) block bacterial translation by binding reversibly to the 16S rRNA in the 30S subunit and distorting it in such a way that the anticodons of the charged tRNAs cannot align properly with the codons of the mRNA.

  5. 3- Chloramphenicol, lincomycin, clindamycin  • These antimicrobials bind to the 50S ribosome and inhibit peptidyltransferase activity. • Chloramphenicol is toxic (bone marrow suppression) but it is used in the treatment of bacterial meningitis.

  6. 4- Macrolides • Macrolides(bacteriostatic) - Erythromycin (also azithromycin, clarithromycin) • The macrolides inhibit translocation of the peptidyltRNA from the A to the P site on the ribosome by binding to the 50S ribosomal 23S RNA.

  7. 5- Fusidic acid • Fusidic acid binds to elongation factor G (EF-G) and inhibits release of EF-G from the EF-G/GDP complex. The elongation factor responsible for moving peptidyl-tRNA from the ribosomal A-site to the P-site during translation. It makes use of a ribosomal GTPase to rotate the small (30S) ribosomal subunit with respect to the large (50S) subunit.

  8. 6- Inhibitors Of RNA Synthesis • Rifampin, rifamycin, rifampicin • These antimicrobials bind to DNA-dependent RNA polymerase and inhibit initiation of RNA synthesis.

  9. 7- Inhibitors of DNA Synthesis • Quinolones- nalidixic acid, ciprofloxacin, oxolinic acid (bactericidal). • These antimicrobials bind to the A subunit of DNA gyrase (topoisomerase) and prevent supercoiling of DNA, thereby inhibiting DNA synthesis.

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