LECTURE 11:
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.
1. Antimicrobials that bind to the 30s Ribosomal Subunit
2. Antimicrobials that bind to the 50s Ribosomal Subunit
3. 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.
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
peptidyl tRNA from the Asite 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 Psite
2- Tetracycline
• The tetracyclines
(tetracycline,
• doxycycline,
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.
3- Chloramphenicol, lincomycin,
clindamycin
• These antimicrobials
bind to the 50S
ribosome and inhibit
peptidyl transferase
activity.
• Chloramphenicol is
toxic (bone marrow
suppression) but it is
used in the treatment
of bacterial meningitis.
4- Macrolides
• Macrolides (bacteriostatic
) - Erythromycin (also
azithromycin,
clarithromycin)
• The macrolides inhibit
translocation of the
peptidyl tRNA from the A
to the P site on the
ribosome by binding to
the 50S ribosomal 23S
RNA.
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 Asite 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.
6- Inhibitors Of RNA Synthesis
• Rifampin, rifamycin, rifampicin
• These antimicrobials bind to DNA-dependent
RNA polymerase and inhibit initiation of RNA
synthesis.
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.