By: Azreena (D11A005) & Nur Nabila (D11A027)

1. By: Azreena (D11A005) & Nur Nabila (D11A027)

2. WHAT IS ANTIBIOTICS? • Also known as antibacterial, the drugs used to treat infections caused by bacteria. • Antibiotics target microorganisms such as bacteria, fungi and parasites. However, they are not effective against viruses. • If antibiotics are overused or used incorrectly there is a chance that the bacteria will become resistant .

3. TRANSCRIPTION • A process where the genetic information in DNA is transferred to a complementary sequence of RNA nucleotides by DNA-RNA polymerase. • 3 Antibiotics that will inhibit TRANSCRIPTION process: • Actinomycin D • Rifampin (Rifampicin or Rifamycin) • Quinolones

4. A) Actinomycin D • Antibiotics that inhibits transcription by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.

5. B) Rifampin (Rifampicin or Rifamycin) • Antibiotics that inhibits protein synthesis by inhibit DNA-RNA polymerase. It does this by binding to the ß subunit of RNA polymerase. • .

6. C) Quinolones • Antibiotics that inhibit the bacterial DNA gyrase or the topoisomerase IV enzyme, thereby inhibiting DNA replication and transcription.

7. EXAMPLES OF QUINOLONES ANTIBIOTICS:

8. Mechanism of Action of Antibiotics

9. Actinomyocin D • Actinomyocin D inhibits initiation of DNA transcription. • It does this by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.

10. Transcription initiation complex

11. Rifampicin • Rifampicin acts directly on messenger RNA synthesis. • It inhibits RNA polymerase in bacterial cells by binding to its beta-subunit, thus preventing transcription to RNA and subsequent translation to proteins. • It inhibits only prokaryotic DNA-primed RNA polymerase, especially those that are Gram-stain-positive . • Its lipophilic nature makes it a good candidate to treat the meningitis form of tuberculosis, which requires distribution to the central nervous system and penetration through the blood-brain barrier.

12. RNA Polymerase

13. Quinolone • Quinolones inhibit bacterial replication by blocking their DNA replication pathway. • Quinolones binds to the A-subunit of the DNA gyrase (Topisomerase II) in Gram-negative bacteria and Topoisomerase IV in Gram-positive bacteria. • This causes the topoisomerase unable to unwind the DNA coiling hence, inhibiting replication and transcription.

15. TASK 2 : LIST DOWN THE ANTIBIOTICS THAT INHIBIT THE PROCESS OF TRANSLATION & EXPLAIN THE MECHANISM OF ITS ACTION TOWARDS INHIBITING THE PATHOGEN INVASION By: Murshida (D11A019) & Fathiyah (D11A006)

16. Antibiotics : • A number of antibiotics act by inhibiting translation are : • Chloramphenicol • Tetracyclines • Macrolides (eg : Erythromycin)

17. CHLORAMPHENICOL Aminoacyl-Trna bound to A site • Antibiotics that inhibits translation by binding to ribosomes and preventing the binding of aminoacylatedtRNA to the A site. • It might also inhibit the peptidyltransferase reaction, preventing the formation of peptide bonds.

18. TETRACYCLINES • Tetracyclines bind to the 30S subunit of microbial ribosomes. • They inhibit protein synthesis by blocking the attachment of chargedaminoacyl-tRNA to the A site on the ribosome.

19. MACROLIDES (ERYTHROMYCIN) • Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit. • The binding inhibits the translocation steps of protein synthesis.

20. Mechanism of Action of Antibiotics

21. INTRODUCTION • Many useful antibiotics owe their action to inhibit some steps in complex process of translation • Their attack always during events occuring on ribosomes,rather than stage of amino acid activation or attachment t particular trna. • Most have affinity to 70s ribosomes • The most important antibitics with this mode of action are tetracyclines,chloramphenicol,macrolides and aminoglycosides

22. Aminoglycosides Mechanism Interfering with translocation by causing misreading of codons along Mrna • Aminoglycosides inhibit translation of Mrna by binding to 30s ribosome causes misreading of codons along Mrna • The misreading of codons causes error in proofreading process of translation leading to improper protein expression

23. Interfering with translocation of tRNA from A site to P site. Aminoglycosides inhibit translation of Mrna by binding irreversibly to 30s subunit of ribosomes. This will inhibit translocation of Trna from A site to P site of ribosomes, preventing elongation of polypeptide chain Lead to incomplete protein expression

24. Tetracyclines Mechanism • Entry of these agents into organism is mediated both by passive diffusion and energy-dependent transport protein mechanism to bacterial inner cytoplasmic membrane. • Tetracyclines binds reversibly to 30s subunit of ribosomes • This prevent binding of aminoacylTrna to A site of ribosome. • The protein synthesise is inhibited.

25. Macrolides mechanism • Microlides bind reversibly to 50S subunit of ribosomes.Some macrolides appear to inhibit elongation of protein by preventing enzyme peptidyltransferase from forming peptide bonds between amino acids. • There is evidence that some prevent transfer of peptidyltRNA from A site to Psite,thus prevent elongation of polypeptide chain.