3.2 BACTERIAL CELL WALL

  Which antibiotics affects peptidoglycan synthesis?

ß-Lactams + Glycopeptides+ Lipopeptides+ Polypeptides+ Amino Acid Analogs 

The bacterial cell wall, specifically the peptidoglycan layer, is a prime target for many antibiotics. The reason being that humans do not have peptidoglycan, which means that drugs targeting this structure can selectively harm bacteria without affecting human cells. Here's a summary of the antibiotics that affect peptidoglycan synthesis:

  • 1. ß-Lactams:These are among the oldest and most widely used antibiotics. Their mechanism of action is by binding to penicillin-binding proteins (PBPs), which are involved in the final steps of peptidoglycan synthesis. This binding inhibits the synthesis and repair of the peptidoglycan layer, leading to bacterial cell lysis and death.

    • The main classes of ß-lactams are:

    • Penicillins+ Cephalosporins+ Carbapenems+ Monobactams 

      • Penicillins (e.g., amoxicillin, penicillin G)

      • Cephalosporins (e.g., cefazolin, ceftriaxone)

      • Carbapenems (e.g., imipenem, meropenem)

      • Monobactams (e.g., aztreonam)

  • 2. Glycopeptides: These large molecules inhibit cell wall synthesis by binding to the D-Ala-D-Ala terminus of the growing peptidoglycan chain, preventing further elongation.

    • E.g. Vancomycin 

      • Vancomycin: The most well-known glycopeptide, it's effective against many Gram-positive bacteria but not Gram-negative bacteria due to its size, which restricts its passage through the Gram-negative outer membrane.

  • 3. Lipopeptides:

    • E.g. Daptomycin

      • Daptomycin: It disrupts multiple bacterial cell functions, including cell wall synthesis, by integrating itself into the bacterial cell membrane.

  • 4. Polypeptides:

    • E.g. Bacitracin 

      • Bacitracin: It targets the bacterial cytoplasmic membrane and interferes with the transport of peptidoglycan precursors from the cytoplasm to the exterior of the cell.

  • 5. Amino Acid Analogs:

    • E.g. Cycloserine 

      • Cycloserine: This is a structural analog of D-alanine, a component of the peptidoglycan layer. By resembling D-alanine, cycloserine interferes with enzymes required for the cross-linking of peptidoglycan chains.


    It's worth noting that the misuse or overuse of these antibiotics can lead to bacterial resistance. Bacteria can alter PBPs, modify their cell walls, or express efflux pumps to reduce the drug's efficacy. As such, it's crucial to use these antibiotics judiciously and in the right clinical contexts.

Antibiotics Affecting Peptidoglycan Synthesis

ß-Lactams

  • Oldest and widely used antibiotics

  • Mechanism of action: Binding to penicillin-binding proteins (PBPs)

  • Inhibits synthesis and repair of peptidoglycan layer

  • Leads to bacterial cell lysis and death

Main Classes of ß-Lactams

  • Penicillins

    • Amoxicillin

    • Penicillin G

  • Cephalosporins

    • Cefazolin

    • Ceftriaxone

  • Carbapenems

    • Imipenem

    • Meropenem

  • Monobactams

    • Aztreonam

Glycopeptides

  • Large molecules

  • Inhibit cell wall synthesis

  • Bind to D-Ala-D-Ala terminus of peptidoglycan chain

  • Prevent further elongation

Example: Vancomycin

  • Effective against Gram-positive bacteria

  • Ineffective against Gram-negative bacteria

  • Restricted passage through Gram-negative outer membrane

Note: Misuse or overuse of these antibiotics can lead to bacterial resistance. Proper usage is crucial.

Lipopeptides

  • Daptomycin

    • Integrates into bacterial cell membrane

    • Disrupts multiple bacterial cell functions

      • Inhibits cell wall synthesis

Polypeptides

  • Bacitracin

    • Targets bacterial cytoplasmic membrane

    • Interferes with transport of peptidoglycan precursors

      • Prevents peptidoglycan synthesis

Amino Acid Analogs

  • Cycloserine

    • Structural analog of D-alanine

    • Interferes with enzymes for peptidoglycan cross-linking

      • Inhibits peptidoglycan synthesis

Note: Misuse or overuse of these antibiotics can lead to bacterial resistance.

  • Bacteria can:

    • Alter penicillin-binding proteins (PBPs)

    • Modify cell walls

    • Express efflux pumps

  • Proper use is crucial for efficacy and preventing resistance.