Undecaprenyl-diphospho-N-acetylmuramoyl-pentapeptide-N-acetylglucosamine (Lipid II) (Lipid II)

Lipid II is an essential, low-abundance intermediate in the biosynthesis of the bacterial peptidoglycan layer, which provides structural integrity to the cell wall [7, 8]. It consists of a MurNAc-GlcNAc-pentapeptide building block attached to a C55-undecaprenyl lipid carrier via a pyrophosphate bridge [7, 9]. As a bottleneck molecule in cell wall assembly, Lipid II is a highly effective target for several classes of antibiotics, including glycopeptides like vancomycin and newer compounds like teixobactin [2, 5, 11]. These drugs typically bind to specific motifs of Lipid II, such as the D-Ala-D-Ala terminus or the pyrophosphate moiety, preventing the incorporation of the precursor into the growing peptidoglycan chain [2, 10]. Because Lipid II is located on the outer leaflet of the cytoplasmic membrane in Gram-positive bacteria, it is accessible to extracellular agents [7, 10]. Its conservation across diverse bacterial species makes it a critical target for treating multi-drug resistant infections [5, 11].

Other names

Undecaprenyl-pyrophosphoryl-MurNAc-(pentapeptide)-GlcNAcBactoprenol-pyrophosphate-MurNAc-pentapeptide-GlcNAcUndecaprenyldiphospho-N-acetyl-(N-acetylglucosaminyl)muramoyl peptidePeptidoglycan precursor Lipid II

Drugs targeting Lipid II primarily inhibit bacterial cell wall synthesis by binding to the precursor and preventing its polymerization into peptidoglycan [2, 10]. Glycopeptides like vancomycin bind the D-alanyl-D-alanine terminus, while others like teixobactin and lantibiotics (e.g., nisin) bind the pyrophosphate or sugar moieties [1, 13, 14]. Some agents, such as nisin and certain lipoglycopeptides, also disrupt the cytoplasmic membrane by forming pores or increasing permeability upon binding to Lipid II [1, 2, 10].