title: Presence of UDP-N-acetylmuramyl-hexapeptides and -heptapeptides in enterococci and staphylococci after treatment with ramoplanin, tunicamycin, or vancomycin.
abstract: Analyses of the peptidoglycan nucleotide precursor contents of enterococci and staphylococci treated with ramoplanin, tunicamycin, or vancomycin were carried out by high-pressure liquid chromatography coupled with mass spectrometry (MS). In all cases, a sharp increase in the UDP-N-actetylmuramoyl-pentapeptide or -pentadepsipeptide pool was observed. Concomitantly, new peptidoglycan nucleotide peptides of higher molecular masses with hexa- or heptapeptide moieties were identified: UDP-MurNAc-pentapeptide-Asp or pentadepsipeptide-Asp in enterococci and UDP-MurNAc-pentapeptide-Gly or -Ala and UDP-MurNAc-pentapeptide-Gly-Gly or -Ala-Gly in staphylococci. These new compounds are derivatives of normal UDP-MurNAc-pentapeptide or -pentadepsipeptide precursors with the extra amino acid(s) linked to the lysine epsilon-amino group as established by various analytical procedures (MS, MS-MS fragmentation, chemical analysis, and digestion with R39 D,D carboxypeptidase). Except for tunicamycin-treated cells, it was not possible to ascertain whether these unusual nucleotides were formed by direct addition of the amino acids to UDP-MurNAc-pentapeptide (or -pentadepsipeptide) or whether they arose by reverse reactions from lipid I intermediates to which the amino acids had been added.
authors.affiliation: LRMA, Université Paris VI, France.
authors.forename: D
authors.initials: D
authors.lastname: Billot-Klein
authors.forename: D
authors.initials: D
authors.lastname: Shlaes
authors.forename: D
authors.initials: D
authors.lastname: Bryant
authors.forename: D
authors.initials: D
authors.lastname: Bell
authors.forename: R
authors.initials: R
authors.lastname: Legrand
authors.forename: L
authors.initials: L
authors.lastname: Gutmann
authors.forename: J
authors.initials: J
authors.lastname: van Heijenoort
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D047630:Depsipeptides; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects* / Q000378:metabolism; D016984:Enterococcus faecium / Q000187:drug effects / Q000378:metabolism; D010456:Peptides, Cyclic; D013210:Staphylococcus / Q000187:drug effects* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000378:metabolism*; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D047630:Depsipeptides; D010456:Peptides, Cyclic; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C041438:ramoplanin; D014415:Tunicamycin; D014640:Vancomycin