Lipid II pyrophosphate moiety (Lipid II) (Lipid II)

Lipid II is an essential, low-abundance intermediate in the bacterial cell wall biosynthetic pathway, serving as the shuttle that transports peptidoglycan building blocks across the cytoplasmic membrane (Schneider & Sahl, 2010). It consists of a MurNAc-pentapeptide-GlcNAc headgroup attached to a C55-undecaprenyl lipid carrier via a pyrophosphate bridge. The pyrophosphate moiety is a highly conserved and accessible target for several classes of potent antibiotics, including lantibiotics like nisin and the recently discovered teixobactin (Ling et al., 2015; Wiedemann et al., 2001). By binding to this specific pyrophosphate region, these drugs sequester Lipid II, preventing its utilization by penicillin-binding proteins (PBPs) for peptidoglycan polymerization. This disruption leads to the loss of cell wall integrity, resulting in rapid bacterial lysis and death. Because the pyrophosphate group is a fundamental structural component rather than a protein-encoded sequence, it is significantly less susceptible to resistance development via target site mutations, making it a high-value target for treating multi-drug resistant Gram-positive infections (Shukla et al., 2023).

Other names

Undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide-GlcNAcBacterial cell wall precursor IILipid IIPeptidoglycan precursor II

Sequestration of Lipid II through high-affinity binding to the pyrophosphate moiety, thereby inhibiting the transglycosylation step of peptidoglycan synthesis and leading to cell lysis.