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.
MeSH Terms
Cells, Cultured
Chromatography, High Pressure Liquid
Dipeptides/analysis
Drug Resistance, Microbial
Enterococcus/drug effects,metabolism
Peptidoglycan/biosynthesis
Uridine Diphosphate N-Acetylmuramic Acid/analogs & derivatives,analysis
Vancomycin/pharmacology
Chemicals
Dipeptides
Peptidoglycan
Uridine Diphosphate N-Acetylmuramic Acid
UDP-N-acetylmuramic acid pentapeptide
alanylalanine
Vancomycin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Billot-Klein D
Laboratoire de Microbiologie Médicale, Université Paris VI, France.
Gutmann L
Collatz E
van Heijenoort J
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