Oct. 16, 2017

Penicillin is a broad-spectrum antibacterial drug, but few of us have considered how this drug performs its primary function. Essentially, penicillin reduces the integrity of bacterial cell walls. Bacteria are constantly replenishing their cell walls when growing or reproducing much like we regenerate our skin. Expansion is accomplished via a network of enzymes and peptidoglycans, the cell wall “bricks”. Penicillin-binding proteins (PBP) belong to a subgroup of enzymes called transpeptidases and are the essential “brick-layers” for bacteria. PBPs catalyze the reaction between peptidoglycans by mediating the removal of D-alanine from the precursor of peptidoglycan. This results in a conformational change and binding of adjacent peptidoglycans. Penicillin acts as an inhibitor for this reaction. The structure of penicillin is very similar to that of the peptidoglycans, so PBP forms a bond with penicillin at the active site. In fact, it’s a covalent bond, so it’s irreversible! PBP is thence rendered inactive, peptidoglycans are left unlinked, and the bacterium’s cell wall is full of holes. Osmotic pressure builds on the bacterium as the cell wall further degrades and eventually leads to cell death. Better them than you! PBPs come in a variety. Pictured here is Penicillin-binding Protein 2a from a resistant strain of Staphylococcus Aureus strain 27r. This bacteria evolved a mutation which allows its PBP2a to resist binding to penicillin. PDB: 1VQQ