Penicillins and Cell-Wall-Synthesis Inhibitors

Introduction

• Cell-wall-synthesis inhibitors block assembly of the bacterial peptidoglycan (murein) wall — the rigid heteropolymer that resists the cell's high internal osmotic pressure; peptidoglycan and its D-alanine chemistry are unique to bacteria, giving these drugs their selective toxicity.
• The β-lactam antibiotics — penicillins, cephalosporins, carbapenems and the monobactam aztreonam — share a β-lactam ring and a common mechanism (inhibition of peptidoglycan cross-linking); they are the single most important antibacterial class.
• Non-β-lactam wall/membrane agents covered here: glycopeptides (vancomycin, teicoplanin), lipoglycopeptides (telavancin, dalbavancin, oritavancin), the lipopeptide daptomycin, and bacitracin.
• Prototype natural penicillin = benzylpenicillin (penicillin G), discovered 1941; near-nontoxic to humans (up to 20 MU/day without organ toxicity).
• Cephalosporins are a separate topic and appear here only in overview for β-lactam-family completeness.