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PMID: 8037690 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Analysis of peptidoglycan precursors in vancomycin-resistant Enterococcus gallinarum BM4174.

The Biochemical journal ·Vol. 301 ( Pt 1) ·1994-07-01 ·Pages 5-8

Reynolds PE, Snaith HA, Maguire AJ, Dutka-Malen S, Courvalin P

Abstract

Vancomycin resistance in enterococci is an increasing clinical problem, and several phenotypes have been identified. We demonstrate here that the resistance mechanism in the constitutively vancomycin-resistant Enterococcus gallinarum BM4174 involves an altered pathway of peptidoglycan synthesis and hydrolysis of the normal precursors in the vancomycin-sensitive pathway. A ligase encoded by the vanC gene catalyses synthesis of D-Ala-D-Ser and substitutes this dipeptide for D-Ala-D-Ala in peptidoglycan precursors. It is presumed that this substitution lowers the affinity of vancomycin for its target site. Destruction of D-Ala-D-Ala (D,D-peptidase activity) and of UDP-MurNAc-L-Ala-D-isoGlu-L-Lys-D-Ala-D-Ala by removal of the terminal D-Ala residue (D,D-carboxypeptidase activity) ensures that the normal vancomycin-sensitive pathway of peptidoglycan synthesis cannot function in the resistant strain.

Related Genes
vanC
MeSH Terms
Amino Acid Sequence Binding Sites Carboxypeptidases/metabolism Drug Resistance, Microbial/genetics Endopeptidases/metabolism Enterococcus/drug effects,genetics,metabolism Genes, Bacterial Molecular Sequence Data Peptidoglycan/genetics,metabolism Phenotype Protein Precursors/genetics,metabolism Vancomycin/pharmacology
Chemicals
Peptidoglycan Protein Precursors Vancomycin Carboxypeptidases Endopeptidases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Reynolds P E
Department of Biochemistry, University of Cambridge, U.K.
Snaith H A
Maguire A J
Dutka-Malen S
Courvalin P
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17 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3010005
Published
1994-07-01
Pages
5-8
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1137133
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3010005 PMC Full Text View journal details
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