Bacterial cells are surrounded by a cell wall made of peptidoglycan (murein): long polysaccharide chains held together by short peptide cross-links. The wall is strong and stops the cell bursting when water enters by osmosis. Human cells have no cell wall, so antibiotics that attack it have high selective toxicity.Penicillin and related β-lactam antibiotics (such as amoxicillin and methicillin) inhibit the transpeptidase enzymes that form the cross-links between peptidoglycan chains. The antibiotic binds to the active site of the enzyme, so new cross-links cannot be made.
A growing bacterium constantly makes new wall, and uses enzymes called autolysins to break some old bonds so the wall can expand. When cross-linking is blocked, the wall becomes weak. Water enters the cell by osmosis, because the cytoplasm has a lower water potential than the surroundings, and the weakened wall cannot resist the pressure. The cell swells and bursts. This is osmotic lysis, so penicillin is bactericidal.Two consequences follow:
• Penicillin works only on bacteria that are actively growing and dividing, since cells that are not making new wall are not affected.
• It is most effective against Gram-positive bacteria, whose thick peptidoglycan wall is exposed on the outside. In Gram-negative bacteria, the thin peptidoglycan layer is protected by an outer membrane that many penicillins cannot cross.Vancomycin also stops peptidoglycan being built, by binding to the building blocks of the wall rather than to the enzyme. It is used against some bacteria that are resistant to penicillins.
A growing bacterium constantly makes new wall, and uses enzymes called autolysins to break some old bonds so the wall can expand. When cross-linking is blocked, the wall becomes weak. Water enters the cell by osmosis, because the cytoplasm has a lower water potential than the surroundings, and the weakened wall cannot resist the pressure. The cell swells and bursts. This is osmotic lysis, so penicillin is bactericidal.Two consequences follow:• Penicillin works only on bacteria that are actively growing and dividing, since cells that are not making new wall are not affected.
• It is most effective against Gram-positive bacteria, whose thick peptidoglycan wall is exposed on the outside. In Gram-negative bacteria, the thin peptidoglycan layer is protected by an outer membrane that many penicillins cannot cross.Vancomycin also stops peptidoglycan being built, by binding to the building blocks of the wall rather than to the enzyme. It is used against some bacteria that are resistant to penicillins.