title: Analysis of peptidoglycan precursors in vancomycin-resistant enterococci.
abstract: Analysis by high-pressure liquid chromatography of the cytoplasmic peptidoglycan precursors of a high- and a low-level vancomycin-resistant Enterococcus spp. was performed before and after induction of resistance. This analysis showed a decrease of the D-Ala-D-Ala and UDP-MurNac-pentapeptide pools, an increase of the UDP-MurNac-tripeptide pool, and the appearance of new UDP-MurNac-containing material. These results lead us to suggest that the vancomycin-induced carboxypeptidase activity cleaves the D-Ala-D-Ala (L. Gutmann, D. Billot-Klein, S. Al-Obeid, I. Klare, S. Francoul, E. Collatz, and J. van Heijenoort, Antimicrob. Agents Chemother. 36:77-80, 1992), which in turn would prevent formation of the normal UDP-MurNac-pentapeptide and thereby of the vancomycin target. The novel UDP-MurNac-containing material is thought to correspond to peptidoglycan precursors which might be synthesized by an alternate pathway (T. D. H. Bugg, G. D. Wright, S. Dutka-Malen, M. Arthur, P. Courvalin, and C. T. Walsh, Biochemistry 30:10408-10415, 1991) and which would be unable to bind vancomycin in glycopeptide-resistant enterococci.
authors.affiliation: Laboratoire de Microbiologie Médicale, Université Paris VI, France.
authors.forename: D
authors.initials: D
authors.lastname: Billot-Klein
authors.forename: L
authors.initials: L
authors.lastname: Gutmann
authors.forename: E
authors.initials: E
authors.lastname: Collatz
authors.forename: J
authors.initials: J
authors.lastname: van Heijenoort
mesh_terms: D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000032:analysis*; D004352:Drug Resistance, Microbial; D016983:Enterococcus / Q000187:drug effects* / Q000378:metabolism; D010457:Peptidoglycan / Q000096:biosynthesis*; D014538:Uridine Diphosphate N-Acetylmuramic Acid / Q000031:analogs & derivatives* / Q000032:analysis*; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D004151:Dipeptides; D010457:Peptidoglycan; D014538:Uridine Diphosphate N-Acetylmuramic Acid; C002225:UDP-N-acetylmuramic acid pentapeptide; C002956:alanylalanine; D014640:Vancomycin