Bacitracin: An Inhibitor of the Dephosphorylation of Lipid Pyrophosphate, an Intermediate in the Biosynthesis of the Peptidoglycan of Bacterial Cell Walls

Bacitraciin is a polypeptide antibiotic produced by certain strainis of Bacillus licheniformis. It inhibits bacterial cell wall synthesis and induces the accumulation in Staphylococcus aureus of UDP-acetylmuramyl-pentapeptide,I a precursor of the cell wall. Recent studies of the detailed mechanism of biosynthesis of the peptidoglycaii of bacterial cell walls have revealed a process that occurs in three stages, viz.: (1) biosynthesis of the uridinie nucleotide precursors, (2) utilization of these precursors to form linear peptidoglycari strands, and (3) cross-linking of the liinearstrands.2 Each of these stages is specifically inhibited by different anti.biotics. Ristocetin, vancomycin, and bacitracin are all inhibitors of the second stage.3 This stage is a complex reaction sequence which occurs in the cell membralle as a consequence of which the sugar fragments of the uridine nucleotide precursors become attached to a phospholipid carrier in the membrane and are then modified. Studies of the individual reactions in this cycle (Fig. 1) have revealed that the re