Mechanism Of Action Of Antibiotics

Question 1

Name the different types of Antibiotics.

Answer 1

• β-lactam
• Quinolone
• Macrolide
• Aminoglycoside
• Tetracycline

Question 2

How do β-lactam Antibiotics function?

Answer 2

• Inhibit Transpeptidase (similar structure to D-alanyl)
• Competitive inhibition
• Irreversible Binding

Question 3

What are Quinolones?

Answer 3

Type: Bactericidal, Synthetic
Spectrum: Broad

Aim: Target Bacterial Enzymes needed for DNA replication (DNA Gyrase)

Structure:

• Bicyclic
• Quinoline backbone (Fusion of Benzene + Pyridine rings)

Examples:
- Ciprofloxacin
- Moxifloxacin

Uses: UTI, respiratory infections

Question 4

What is the Quinolones Mechanism of Action?

Answer 4

Quinolones diffuse into Bacterial Cell + Bind with high affinity to A subunit of DNA Gyrase (Topoisomerase II) in Gram-Negatives and to Topoisomerase IV in Gram-Positives.

By stabilizing Gyrase–DNA or Topo IV–DNA cleavage complex, they prevent the controlled ligation step of supercoiling

Accumulation of DNA breaks: “Trapping” leads to persistent single- and double-stranded DNA breaks.

Extensive DNA Fragmentation + Failed Repair Cause Irreversible Loss of Genomic Integrity and Rapid Cell Death

Question 5

What Are Macrolides?

Answer 5

• Bacteriostatic Agents with Macrocyclic lactone ring
• Polyketides (Natural products)

Question 6

What is the Spectrum of Activity of Macrolides?

Answer 6

• Against Gram+ cocci
• Staphylococci + Streptococci

Others:
- Mycobacteria
- Mycoplasmas
- Spirochetes

Question 7

What is The Mechanism Of Action of Macrolides?

Answer 7

Macrolides Passively Diffuse Across Bacterial Cell Envelope—Through Porins In Gram- , Directly through Cytoplasmic Membrane in Gram+

Once inside, Macrolides Bind To 23S rRNA Component of 50S Ribosomal Subunit, Lodging Deep Within Nascent Peptide Exit Tunnel

“Plugging” Prevents Growing Polypeptide Chain From Passing Through Ribosome, Halting Translation Elongation

Stalled Ribosome–tRNA–mRNA Complex Leads To Premature Dissociation of Peptidyl-tRNA, so incomplete peptides drop off and cannot be rescued.

By freezing protein synthesis, Macrolides stop Bacterial Growth

• Disrupt bacterial communities
• Inhibit pro-inflammatory cytokines
• Reduce neutrophil recruitment to inflamed tissues

Question 8

What are the Aminoglycosides?

Answer 8

• Bactericidal
• Amino sugars bonded by Glycosidic Bonds (Natural Products)

Question 9

What is the Spectrum Of Activity of Aminoglycosides?

Answer 9

Gram Negative
- Streptomycin
- Kanamycin
- Tobramycin
- Gentamycin
- Neomycin

Question 10

What Is The Mechanism Of Action of Aminoglycosides?

Answer 10

Disrupt Bacterial Protein Synthesis

1. Irreversibly bind to 16S rRNA within the 30S Ribosomal subunit at A-Site
2. Ribosome structure distorted, Mis-interprets mRNA codons
3. Amino acids mis-incorporated in elongating peptides
4. Incorporation of misfolded proteins causes membrane damage, increasing permeability, causing increased drug uptake
5. Ribosome targeting and binding increases
6. Causes Cell Death

Question 11

What Are Tetracyclines?

Answer 11

• Bacteriostatic Antibac agents
• Natural products

Question 12

What is The Spectrum Of Activity of Tetracyclines?

Answer 12

• Broad spectrum
• Work better against Gram+

Examples:
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Staphylococcus aureus

Question 13

What Is The Mechanism Of Action of Tetracyclines?

Answer 13

Inhibit Protein Synthesis

1. Bind to 16S rRNA near A site
2. Aminoacyl-tRNA binding to A site stopped
3. tRNA unable to dock or add amino acids to growing polypeptide chain
4. Elongation halted
5. Bacterial Replication Arrested