Bacterial lipid II (Lipid II) (Lipid II)

Bacterial lipid II is a critical, rate-limiting intermediate in the biosynthesis of the bacterial cell wall peptidoglycan (Breukink & de Kruijff, 2006). It consists of a disaccharide-pentapeptide building block linked to a C55-undecaprenyl lipid carrier through a pyrophosphate bridge (Schneider & Sahl, 2010). Synthesized on the cytoplasmic side of the inner membrane, Lipid II is translocated to the periplasmic space where it is incorporated into the growing peptidoglycan polymer by transglycosylases and transpeptidases (Müller et al., 2017). Due to its essential role and high conservation across Gram-positive and Gram-negative bacteria, it serves as a highly effective target for various antibiotic classes (Ling et al., 2015). Drugs like vancomycin bind to the D-alanyl-D-alanine terminus of the pentapeptide, while newer agents like teixobactin target the pyrophosphate-sugar moiety (Oppedijk et al., 2016). By sequestering Lipid II, these antibiotics halt cell wall assembly, leading to membrane instability and bacterial cell death (Grein et al., 2020).

Other names

Undecaprenyl-pyrophosphoryl-MurNAc-pentapeptide-GlcNAcPeptidoglycan precursor lipid IILipid 2Undecaprenyl-diphospho-N-acetylmuramoyl-pentapeptide-N-acetylglucosamine

Antibiotics target Lipid II through several distinct mechanisms: glycopeptides (e.g., vancomycin) bind the D-Ala-D-Ala terminus of the pentapeptide; lantibiotics (e.g., nisin) and teixobactin bind the pyrophosphate/sugar moiety; and others like ramoplanin bind the carbohydrate headgroup. These interactions sequester the precursor, preventing its utilization by penicillin-binding proteins (PBPs) for peptidoglycan polymerization (Breukink & de Kruijff, 2006; Ling et al., 2015).