Affiliation:
1. Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom,1 and
2. Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris, Cedex 15, France2
Abstract
ABSTRACT
Glycopeptide-resistant enterococci of the VanC type synthesize UDP-muramyl-pentapeptide[
d
-Ser] for cell wall assembly and prevent synthesis of peptidoglycan precursors ending in
d
-Ala. The
vanC
cluster of
Enterococcus gallinarum
BM4174 consists of five genes:
vanC-1
,
vanXY
C
,
vanT
,
vanR
C
, and
vanS
C
. Three genes are sufficient for resistance:
vanC-1
encodes a ligase that synthesizes the dipeptide
d
-Ala-
d
-Ser for addition to UDP-MurNAc-tripeptide,
vanXY
C
encodes a
d
,
d
-dipeptidase–carboxypeptidase that hydrolyzes
d
-Ala-
d
-Ala and removes
d
-Ala from UDP-MurNAc-pentapeptide[
d
-Ala], and
vanT
encodes a membrane-bound serine racemase that provides
d
-Ser for the synthetic pathway. The three genes are clustered: the start codons of
vanXY
C
and
vanT
overlap the termination codons of
vanC-1
and
vanXY
C
, respectively. Two genes which encode proteins with homology to the VanS-VanR two-component regulatory system were present downstream from the resistance genes. The predicted amino acid sequence of VanR
C
exhibited 50% identity to VanR and 33% identity to VanR
B
. VanS
C
had 40% identity to VanS over a region of 308 amino acids and 24% identity to VanS
B
over a region of 285 amino acids. All residues with important functions in response regulators and histidine kinases were conserved in VanR
C
and VanS
C
, respectively. Induction experiments based on the determination of
d
,
d
-carboxypeptidase activity in cytoplasmic extracts confirmed that the genes were expressed constitutively. Using a promoter-probing vector, regions upstream from the resistance and regulatory genes were identified that have promoter activity.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
74 articles.
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