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Thursday, March 12, 2009

article : Mechanism of Action of Beta-Lactam Antibiotics

Structures of Beta-Lactam Antibiotics:

Bactericidal Against Actively Growing Cells

Drug Covalently Links to Cytoplasmic Membrane Regulatory Enzymes (a.k.a., Penicillin binding proteins (PBP))

PBPs function in cell to catalyze crosslinking of peptidoglycan chains

PBPs are transpeptidases

Beta-Lactam Antibiotics at Concentrations >MIC:

Bind to PBPs

Disrupt synthesis of peptidoglycan

Resultant release of autolysins (autolytic enzymes)

Autolysins enzymatically degrade cell wall forming spheroplast (osmotically-sensitive cell lacking rigidity of cell wall)

Cells lyse; Bacterial cell killed

For E. coli, at Concentrations <MIC:

Septum formation is interrupted

Filamentous, multinucleated cells are observed with cells continuing to divide but septa (new cell walls that separate daughter cells) do not form

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