Modified peptidoglycan precursors produced by glycopeptide-resistant enterococci.
Cytoplasmic precursors of the peptidoglycan biosynthetic pathway were purified from vancomycin-treated, glycopeptide-sensitive and -resistant strains of Enterococcus faecium. Resistance was due to production of a modified precursor, UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate, where lactate was identified on the basis of mass of the precursor and on its ability to act as a substrate for D-lactate dehydrogenase after release from the precursor. The presence of the D-lactate residue instead of D-alanine in the terminal position would hinder formation of a vancomycin-precursor complex, without preventing incorporation of the precursor into mature peptidoglycan.
Messer
J
J
Department of Biochemistry, University of Cambridge, UK.
Reynolds
P E
PE
D000595:Amino Acid Sequence; D002473:Cell Wall / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects / Q000378:metabolism*; D006020:Glycopeptides / Q000494:pharmacology*; D006595:Hexosamines / Q000032:analysis; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000096:biosynthesis*; D011498:Protein Precursors / Q000096:biosynthesis*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives / Q000032:analysis; D014640:Vancomycin / Q000494:pharmacology
D006020:Glycopeptides; D006595:Hexosamines; D010457:Peptidoglycan; D011498:Protein Precursors; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C076611:UDP-N-acetylmuramyl-Ala-Glu-Lys-Ala-lactate; D014640:Vancomycin