Undecaprenyl pyrophosphate and Lipid II intermediates (UPP/Lipid II)

Bacterial peptidoglycan synthesis lipid pyrophosphate intermediates, most notably undecaprenyl pyrophosphate (C55-PP) and Lipid II, are essential molecules in the construction of the bacterial cell wall. These intermediates function as a lipid shuttle, where the C55-isoprenoid chain anchors hydrophilic cell wall building blocks and facilitates their transport across the hydrophobic cytoplasmic membrane (Müller et al., 2017). Once the building block is delivered to the growing peptidoglycan layer, the remaining undecaprenyl pyrophosphate must be dephosphorylated to undecaprenyl phosphate to be recycled for further rounds of transport (Stone & Strominger, 1971). Because these molecules are highly conserved across various bacterial species and are absent in mammalian cells, they represent ideal targets for antimicrobial therapy. Antibiotics such as vancomycin and teixobactin bind directly to Lipid II, effectively sequestering the precursor and preventing its incorporation into the cell wall, which leads to cell lysis and death (Ling et al., 2015). Other agents, like bacitracin, interfere with the recycling process by binding to the pyrophosphate group of C55-PP, thereby depleting the pool of available lipid carriers (Stone & Strominger, 1971). These targets are particularly valuable in the fight against multi-drug resistant pathogens, as the pyrophosphate and sugar moieties they contain are less prone to mutational changes compared to protein targets.

Other names

Bactoprenyl pyrophosphateUndecaprenyl diphosphateLipid ILipid IIC55-isoprenyl pyrophosphateC55-PP

Inhibition of peptidoglycan synthesis by sequestering lipid-linked precursors or preventing the recycling of the undecaprenyl phosphate carrier.