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.