The cytoplasmic peptidoglycan precursor of vancomycin-resistant Enterococcus faecalis terminates in lactate.
Vancomycin resistance plasmids in enterococci carry the genes vanH and vanA, which encode enzymes catalyzing, respectively, the reduction of 2-keto acids to 2-D-hydroxy acids and the addition of D-hydroxy acids to D-alanine. It has therefore been postulated that resistant cells produce peptidoglycan precursors that terminate in the depsipeptide D-alanine-2-D-hydroxy acid rather than the dipeptide D-alanine-D-alanine, thus preventing vancomycin binding (M. Arthur, C. Molinas, T. D. H. Bugg, G. D. Wright, C. T. Walsh, and P. Courvalin, Antimicrob. Agents Chemother. 36:867-869, 1992). In the present work, a cytoplasmic peptidoglycan precursor was isolated from vancomycin-resistant Enterococcus faecalis and analyzed by mass spectrometry, which suggested the structure UDP-N-acetyl-muramyl-L-Ala-D-Glu-L-Lys-D-Ala-D-lactate.
Handwerger
S
S
Division of Infectious Diseases, Beth Israel Medical Center, Mount Sinai School of Medicine, New York, New York 10003.
Pucci
M J
MJ
Volk
K J
KJ
Liu
J
J
Lee
M S
MS
D000595:Amino Acid Sequence; D003593:Cytoplasm / Q000737:chemistry; D004352:Drug Resistance, Microbial; D013293:Enterococcus faecalis / Q000737:chemistry*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000096:biosynthesis / Q000737:chemistry*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification; D014640:Vancomycin / Q000494:pharmacology*
D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C076611:UDP-N-acetylmuramyl-Ala-Glu-Lys-Ala-lactate; D014640:Vancomycin