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

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 .

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:

A) Actinomycin DB) Rifampin (Rifampicin or Rifamycin)C) Quinolones

A) Actinomycin D

• Antibiotics that inhibits transcription by binding DNA at the transcription initiation complex and preventing elongation by RNA polymerase.

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.

• .

C) Quinolones

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

EXAMPLES OF QUINOLONES ANTIBIOTICS:

Mechanism of Action of Antibiotics

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.

Transcription initiation complex

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.

RNA Polymerase

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.

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)

Antibiotics :

• A number of antibiotics act by inhibiting translation are :

1) Chloramphenicol

2) Tetracyclines

3) Macrolides (eg : Erythromycin)

CHLORAMPHENICOL

• Antibiotics that inhibits translation by binding to ribosomes and preventing the binding of aminoacylated tRNA to the A site.

• It might also inhibit the peptidyl transferase reaction, preventing the formation of peptide bonds.

Aminoacyl-Trnabound to A site

TETRACYCLINES

• Tetracyclines bind to the 30S subunit of microbial ribosomes.

• They inhibit protein synthesis by blocking the attachment of charged aminoacyl-tRNA to the A site on the ribosome.

MACROLIDES (ERYTHROMYCIN)

• Inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit.

• The binding inhibits the translocation steps of protein synthesis.

Mechanism of Action of Antibiotics

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

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

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 chainLead to incomplete protein expression

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 aminoacyl Trna to A site of ribosome.

• The protein synthesise is inhibited.

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 peptidyl tRNA from A site to Psite,thus prevent elongation of polypeptide chain.