title: The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation.
abstract: The lantibiotic mersacidin has been previously reported to interfere with bacterial peptidoglycan biosynthesis, [Brötz, H., Bierbaum, G., Markus, A., Molitor, E. & Sahl, H.-G. (1995) Antimicrob. Agents Chemother. 39, 714-719]. Here, we focus on the target reaction and describe a mersacidin-induced accumulation of UDP-N-acetylmuramoyl-pentapeptide, indicating that inhibition of peptidoglycan synthesis occurs after the formation of cytoplasmic precursors. In vitro studies involving a wall-membrane particulate fraction of Bacillus megaterium KM demonstrated that mersacidin did not prevent the synthesis of lipid II [undecaprenyl-diphosphoryl-N-acetylmuramoyl-(pentapeptide)-N-ac ety lglucosamine] but specifically the subsequent conversion of this intermediate into polymeric nascent glycan strands by transglycosylation. Comparison with other inhibitors of transglycosylation shows that the effective concentration of mersacidin in vitro is in the range of that of the glycopeptide antibiotic vancomycin but 2-3 orders of magnitude higher than that of the competitive enzyme inhibitor moenomycin. The analogy to the glycopeptides may hint at an interaction of mersacidin with the peptidoglycan precursor rather than with the enzyme. Unlike vancomycin however, mersacidin inhibits peptidoglycan formation from UDP-N-acetylmuramoyl-tripeptide and is active against Enterococcus faecium expressing the vanA resistance gene cluster. This indicates that the molecular target site of mersacidin differs from that of vancomycin and that no cross-resistance exists between the two antibiotics.
authors.affiliation: Institut für Medizinische Mikrobiologie und Immunologie, Universität Bonn, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Brötz
authors.forename: G
authors.initials: G
authors.lastname: Bierbaum
authors.forename: P E
authors.initials: PE
authors.lastname: Reynolds
authors.forename: H G
authors.initials: HG
authors.lastname: Sahl
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001410:Bacillus megaterium / Q000187:drug effects / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D001430:Bacteriocins; D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016983:Enterococcus / Q000187:drug effects; D006031:Glycosylation / Q000187:drug effects; D008563:Membrane Lipids / Q000032:analysis; D008969:Molecular Sequence Data; D009112:Muramic Acids / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010455:Peptides; D010457:Peptidoglycan / Q000096:biosynthesis*; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; C096686:FemA protein, Bacteria; C102928:FemB protein, Staphylococcus epidermidis; D008563:Membrane Lipids; D009112:Muramic Acids; D010455:Peptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C069959:mersacidin; C002225:UDP-N-acetylmuramic acid pentapeptide; D014537:Uridine Diphosphate N-Acetylglucosamine; C012993:gardimycin; D014640:Vancomycin