This document summarizes the mechanisms of action of various protein synthesis inhibitors in bacteria. It discusses how these inhibitors target different stages of mRNA translation in the bacterial ribosome, including initiation, elongation, and termination. Some key inhibitors mentioned are aminoglycosides, spectinomycin, linezolid, tetracyclines, chloramphenicol, macrolides, clindamycin, streptogramins, and mupirocin. They act by binding to different sites on the bacterial ribosomal subunits and disrupting proper formation of initiation complexes, misreading of mRNA, peptide bond formation, and translocation during translation.

1. Dr.Elza Joy Munjely
JR-I
Depmt. Of Pharmacology
Govt. Medical College,Kottayam.

2. 2
INTRODUCTION TO PROTEIN
SYNTHESIS
• Protein synthesis inhibitor - substance that stops or
slows the growth or proliferation of bacterial cells by
disrupting the processes of generation of new proteins by
targeting the bacterial ribosome.
• Act at the ribosome level
• Take advantage of the major differences between
prokaryotic and eukaryotic ribosome.
• Work at different stages of mRNA translation like
initiation, elongation, and termination.

3. 3
PROKARYOTIC AND EUKARYOTIC RIBOSOMES

4. PROTEIN SYNTHESIS

5. PROCESS OF TRANSLATION

7. 30 S
50S
P-Site A-Site
INITIATION COMPLEX
m-RNA

8. A4
P-Site A-Site
A3
A2
A1
TRANSPEPTIDATION

9. A4
P-Site A-Site
A3
A2
A1

10. A4
A3
A2
A1

11. A4
A3
A2
A1
A
5
TRANSLOCATION

12. A4
A3
A2
A1
A
5
TRANSLOCATION

13. A4
A3
A2
A1
A
5
A
6

14. MOA OF AMINOGLYCOSIDES &
SPECTINOMYCIN
 Penetrate bacterial cell wall through porin channels by
passive diffusion
 Betalactams facilitate passive diffusion of
aminoglycosides-SYNERGISTIC ACTION
Bind to 30S ribosomal subunit
Improper formation of initiation complex
Misreading of mRNA

15. 30 S
50S
P-Site A-Site
IMPROPER FORMATION OF INITIATION
COMPLEX & MISREADING OF mRNA
m-RNA
AMINOGLYCOSIDES
&SPECTINOMYCIN

16. MOA OF LINEZOLID
 Binds to 50S ribosomal subunit near the interface with
30S subunit.
 Prevents the formation of ribosomal complex.

17. 50S
P-Site A-Site
LINEZOLID
INHIBITION OF RIBOSOMAL COMPLEX
FORMATION

18. MOA OF TETRACYCLINES
 Drug enter into cytoplasm by:
 Energy dependent tetracycline active transport system –
Gram positive bacteria
 Passive diffusion through porin channels – Gram
negative bacteria
 Binds to 30Ssubunit of the ribosome
 & inhibits the binding of aminoacyl tRNA to the A site.

19. A4
P-Site A-Site
A3
A2
A1
TETRACYCLINES
PREVENTS BINDING OF AMINOACYL tRNA
TO A SITE

20. MOA OF CHLORAMPHENICOL
 Binds to 50S subunit of the ribosome
 Inhibits peptide bond formation.

21. A4
P-Site A-Site
A3
A2
A1
TRANSPEPTIDATION
INHIBITED
CHLORAMPHENICOL

22. MOA OF MACROLIDES ,CLINDAMYCIN
&STREPTOGRAMINS
 Reversibly binds to P site of 50 S ribosome
 Thus inhibits translocation

23. A4
A3
A2
A1
P-Site A-Site
MACROLIDES ,
CLINDAMYCIN &
STREPTOGRAMINS
TRANSLOCATION INHIBITED

24. MOA OF MUPIROCIN
 Binds to isoleucyl tRNA synthetase
 Prevents incorporation of isoleucine into bacterial
protiens

25. THANK YOU