Lecture Notes: Cell Wall Synthesis in Bacteria and Antibiotics

Introduction to Cell Wall Synthesis as an Antibiotic Target

• Cell wall synthesis in bacteria is a target for antibiotics due to low host toxicity.
• Humans do not have peptidoglycan, making it an ideal target.

Beta-Lactam Antibiotics

• Most cell wall targeting antibiotics contain a beta-lactam ring.
• Common beta-lactam drugs include penicillins and cephalosporins.

Historical Background

• Penicillin G
  • First beta-lactam antibiotic.
  • Discovered by Alexander Fleming in 1929 from Penicillium chrysogenum fungus.
  • Initially difficult to isolate; Fleming struggled to gain recognition for its importance.
  • Progress made in 1940 by Howard Florey and colleagues, highlighting its functionality.

Functionality of Penicillin

• Penicillin G
  • Primarily effective against gram-positive bacteria (e.g., streptococci, pneumococcal infections).
  • Ineffective against gram-negative bacteria due to impermeability issues.

Semi-Synthetic Penicillins

• Developed from penicillin G by altering side groups.
• Some semi-synthetic variants can cross the outer membrane, making them effective against gram-negative bacteria.

Mechanism of Action

• Beta-lactams are analogs of terminal amino residues in pentapeptide glycan subunits.
• Structural similarity facilitates binding to transpeptidases (penicillin-binding proteins or PBPs).
  • Prevents the cross-linking step during cell wall synthesis.
  • Results in a compromised cell wall due to lack of cross-linking.

Impact on Bacterial Cells

• Binding to penicillin-binding proteins inhibits catalysis of cell wall reactions.
• Stimulates release of autolysins, enhancing degradation of existing cell wall.
• Leads to a weakened cell wall and eventual cell lysis due to osmotic pressure.

Conclusion

• Beta-lactam antibiotics play a crucial role in disrupting bacterial cell wall synthesis, leading to bacterial cell death, particularly in gram-positive bacteria.