Bacterial cell wall precursor Lipid II (Lipid II)

Bacterial cell wall precursor Lipid II is an essential, low-abundance intermediate in the biosynthesis of peptidoglycan, the primary structural component of the bacterial cell wall (Münch & Sahl, 2015, Nature Reviews Microbiology). It consists of a disaccharide (N-acetylglucosamine and N-acetylmuramic acid) with a pentapeptide chain, linked to a C55 undecaprenyl lipid carrier via a pyrophosphate bridge (Breukink & de Kruijff, 2006, Nature Reviews Drug Discovery). Lipid II is synthesized on the inner leaflet of the cytoplasmic membrane and subsequently flipped to the outer leaflet, where it serves as the substrate for transglycosylases and transpeptidases (Schneider & Sahl, 2010, Applied Microbiology and Biotechnology). Because Lipid II is highly conserved across Gram-positive and Gram-negative bacteria and is vital for maintaining cell integrity, it is a prime target for various antibiotic classes. Drugs like vancomycin bind to the D-Ala-D-Ala terminus of the pentapeptide, while newer agents like teixobactin target the pyrophosphate and sugar moieties, effectively halting cell wall construction and leading to bacterial lysis (Ling et al., 2015, Nature). Its role as a bottleneck in cell wall synthesis makes it an effective target for overcoming certain types of antibiotic resistance.

Other names

Undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAcLipid 2Bactoprenol-pyrophosphate-MurNAc-pentapeptide-GlcNAcPeptidoglycan precursor Lipid II

Inhibition of cell wall synthesis by binding to the Lipid II precursor, thereby blocking the transglycosylation and transpeptidation steps of peptidoglycan polymerization.