Beta-lactams, penicillin-binding proteins and cell wall synthesis
Beta-lactam antibiotics block penicillin-binding proteins, the enzymes that cross-link (join together) the sugar chains of peptidoglycan, the mesh that forms the bacterial cell wall.
Remember
Beta-lactams attach to penicillin-binding proteins, so peptidoglycan is not cross-linked, the wall is weak and the bacteria burst (this is called lysis), especially while they are actively growing.
Memory aid
the PBPs are the builders who tie the wall mesh together, and beta-lactams stop them tying it
Remember that the penicillin-binding proteins are the builders tying the wall mesh together, and that beta-lactams stop them.
Bacteria are surrounded by a wall of peptidoglycan. Its sugar chains are cross-linked by short peptide bridges, which gives the wall strength and stops the cell bursting under its own internal pressure. The cross-linking is done by enzymes called penicillin-binding proteins.
The beta-lactam antibiotics are an umbrella group of four families: penicillins, cephalosporins, carbapenems and monobactams. They are named for the beta-lactam ring in their structure. Amoxicillin is a penicillin, and like other beta-lactams it blocks the penicillin-binding proteins.
Beta-lactams bind and block these enzymes. Newly made wall is then weak, water floods in and the cell bursts. This happens especially in bacteria that are actively growing and making new wall. Beta-lactams block the final stage of wall construction, the cross-linking.
Because the drugs kill bacteria rather than just halting their growth, they are bactericidal. A bacteriostatic drug slows or stops growth and reproduction.
Human cells do not make peptidoglycan, so beta-lactams are selectively toxic: they harm the bacterium far more than the patient, and they are generally well tolerated.
Key facts
- Target
- penicillin-binding proteins, the enzymes that cross-link peptidoglycan.
- Families
- penicillins, cephalosporins, carbapenems and monobactams.
- Result
- the new wall is weak, water floods in and the cell bursts (lysis).
- Killing
- the drugs are bactericidal: they kill bacteria rather than just halting their growth.
- Safety
- human cells have no peptidoglycan, so the drugs are selectively toxic to bacteria.
- Classes that act on the wall
- beta-lactams, and also the glycopeptides (another class of antibiotics) such as vancomycin.
Exam traps
- Aminoglycosides (antibiotics such as gentamicin) are bactericidal too, which can make them seem like wall inhibitors. Their target is the 30S subunit, the smaller half of the ribosome (the machine that builds proteins), so they act on protein synthesis and not on the wall.
- Macrolides (antibiotics such as erythromycin) bind the 50S subunit, the larger half of the ribosome, and inhibit protein synthesis. They are mainly bacteriostatic and do not inhibit the wall-building enzymes that beta-lactams target.
- Fluoroquinolones (antibiotics such as ciprofloxacin) block DNA gyrase, an enzyme that manages the coiling of bacterial DNA so that it can be copied. They stop DNA replication and leave the wall alone.
Read the full notes
Tested in 14 SimpleMed+ questions
Practice it in Infection, with the answer and a full explanation after every question.
Practice these questions