Beta-lactam mechanism of action
Beta-lactam antibiotics, named after a four-membered ring, bind penicillin-binding proteins, enzymes that cross-link (join) chains of peptidoglycan, the mesh forming the bacterial cell wall.
Remember
Beta-lactams bind penicillin-binding proteins and block peptidoglycan cross-linking, so the bacterial wall fails and the cell lyses (bursts). They are bactericidal, meaning they kill bacteria rather than only halting growth.
Memory aid
Picture the cell wall as brickwork
The peptidoglycan strands are the bricks, the cross-links are the mortar, and beta-lactams remove the mortar.
All beta-lactam antibiotics share a four-membered beta-lactam ring, and this ring is the working part of the drug. It lets the drug bind the penicillin-binding proteins (PBPs), which are transpeptidase enzymes (enzymes that join two chains together) that help to build the bacterial wall.
The wall is made of peptidoglycan, a mesh of sugar chains and short peptide bridges that holds the cell together against the pressure of the fluid inside it. The PBPs build the cross-links in this mesh. When a beta-lactam blocks them, the new wall has no cross-links, so it is weak.
A bacterium sits at a high internal osmotic pressure, because water is constantly drawn into the cell. A weakened wall fails under this pressure, so the cell swells and bursts. That bursting is called osmotic lysis. Because the cell is killed rather than simply held back, beta-lactams are bactericidal.
Their killing is time-dependent: what matters is how long the drug level stays above the minimum inhibitory concentration (the lowest concentration that stops visible growth). That is why many beta-lactams are given several times a day.
Human cells make no peptidoglycan, so the drugs are selectively toxic to bacteria. Glycopeptides (vancomycin and teicoplanin) also block wall assembly, but they bind the peptidoglycan precursors (the building blocks of the wall) rather than the PBPs.
Key facts
- Target
- penicillin-binding proteins, which act as transpeptidases (enzymes that join two chains together) and cross-link peptidoglycan.
- Family
- the four sub-classes are the penicillins, cephalosporins, carbapenems and monobactams (for example flucloxacillin, ceftriaxone, meropenem and aztreonam).
- Effect
- a weakened wall, osmotic lysis and bacterial death, so the action is bactericidal.
- Dosing
- killing is time-dependent, so the doses of many beta-lactams are repeated through the day.
- Human cells
- they make no peptidoglycan, so the drugs are selectively toxic to bacteria.
- Near miss
- glycopeptides such as vancomycin also block wall assembly, but they bind the precursors, not the PBPs.
Exam traps
- Stopping peptidoglycan cross-linking does not by itself point to a beta-lactam, because glycopeptides such as vancomycin and teicoplanin also do it. They bind the peptidoglycan precursors (its building blocks), whereas beta-lactams bind the penicillin-binding proteins.
- Blocking the 30S ribosomal subunit is how the antibiotic classes aminoglycosides and tetracyclines stop the cell making proteins. Beta-lactams do not act on the ribosome, because their target is the enzymes that build the wall.
- Inactivation of beta-lactamase enzymes (enzymes some bacteria make that break open the beta-lactam ring) is the job of a helper such as clavulanic acid, which protects its partner penicillin. It does not describe how a beta-lactam itself kills bacteria.
Read the full notes
Tested in 8 SimpleMed+ questions
Practice it in Pharmacology, with the answer and a full explanation after every question.
Practice these questions