Beta-lactam antibiotics (penicillin, methicillin, oxacillin) kill bacteria by binding the active site of penicillin-binding proteins (PBPs) — transpeptidase enzymes that crosslink peptide bridges between glycan strands to build the peptidoglycan sacculus, the mesh that keeps the cell from bursting under osmotic pressure. This view unrolls that cylindrical mesh flat: each horizontal line is one glycan strand (always intact — the drug does not touch these bonds), and each vertical rod is a peptide crosslink between consecutive strands, staggered row-to-row exactly as real murein sacculi are drawn in textbooks.
MRSA carries the mobile genetic element SCCmec with the mecA gene, encoding an alternative transpeptidase, PBP2a, whose active site has drastically lower affinity for beta-lactams. Per exposure cycle, the probability a given crosslink site's PBP is knocked out by the drug is modelled as:
P(inhibit) = 1 − e^(−k · C)
k(normal PBP) ≈ 0.8 (high affinity)
k(PBP2a) ≈ 0.0008 (~1000× lower affinity)
C = antibiotic concentration, in multiples of the MIC
Wall integrity evolves from the balance between PBP-driven crosslink synthesis and constant autolysin-mediated remodelling:
crosslink fraction = (1−r)·[1−P(inhibit)_normal] + r·[1−P(inhibit)_PBP2a]
dIntegrity/dt = k_synth · crosslink_fraction − k_autolysin
r = mecA / PBP2a expression fraction
k_synth = 9, k_autolysin = 7 (equilibrium at crosslink fraction = 7/9 ≈ 78%)
At high antibiotic concentration with r = 0 (MSSA), nearly every normal PBP is inhibited, crosslink fraction collapses well below the 78% equilibrium point, autolysins outpace synthesis, and wall integrity falls to zero — lysis. With r near 1 (MRSA), most transpeptidase activity runs through PBP2a, which the drug barely touches, so crosslinking stays near its equilibrium and the cell survives even at concentrations many multiples above the MIC for a susceptible strain. This is exactly why methicillin/oxacillin — and every other beta-lactam except the newest anti-MRSA cephalosporins — fail against MRSA, and why vancomycin (a different, cell-wall-precursor-binding mechanism) became the historical fallback.
- Concentration slider — beta-lactam dose in multiples of the MIC for a fully susceptible strain.
- mecA / PBP2a slider — fraction of transpeptidase activity running through the resistant PBP2a instead of native PBPs (heteroresistant populations sit between 0 and 100%).
- Presets — MSSA loads r = 0%, MRSA loads r = 95%.
- Green vertical rods are intact peptide crosslinks; red rods are sites currently inhibited by the drug. Small tumbling triangles are antibiotic molecules, scaled to concentration. The strip chart below the mesh traces integrity (green) and crosslink density (amber) over time.
- Drag the mesh to pan, scroll/pinch to zoom — the lattice extends beyond the viewport once magnified so you can inspect individual crosslink sites.