Lipid II and other bactoprenol-bound cell wall precursors as drug targets.
Bacterial cell wall biosynthesis represents an antibiotic target pathway for therapeutic intervention. An increasing number of natural antibiotic compounds have been demonstrated to inhibit the membrane-associated steps of cell wall biosynthesis by targeting bactoprenol-mediated precursor cycling, particularly at the stage of the completed building block Lipid II. These antibiotic compounds belong to various chemical classes including glycopeptides, lipopeptides and lipodepsipeptides, and lantibiotics and other antimicrobial peptides. The clinical success of vancomycin in the treatment of multiresistant Gram-positive bacteria has stimulated further development of glycopeptide antibiotics and research of other Lipid II-binding compounds. The state-of-the-art in the targeting of cell wall precursors is summarized in this review.
Schneider
Tanja
T
University of Bonn, Institute of Medical Microbiology, Immunology and Parasitology, Pharmaceutical Microbiology Section, Meckenheimer Allee 168, 53115 Bonn, Germany.
Sahl
Hans-Georg
HG
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002473:Cell Wall / Q000378:metabolism; D016503:Drug Delivery Systems; D024901:Drug Resistance, Multiple, Bacterial; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D013729:Terpenes / Q000378:metabolism; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013729:Terpenes; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069249:muramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenol; C000146:bactoprenol; D014640:Vancomycin