Affiliation:
1. Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris, Cedex 15, France
2. Department of Biochemistry, University of Cambridge, Cambridge CB21QW, United Kingdom
Abstract
ABSTRACT
VanD type
Enterococcus faecium
10/96A is constitutively resistant to vancomycin and to low levels of teicoplanin by nearly exclusive synthesis of peptidoglycan precursors terminating in
d
-alanyl-
d
-lactate (L. M. Dalla Costa, P. E. Reynolds, H. A. Souza, D. C. Souza, M. F. Palepou, and N. Woodford, Antimicrob. Agents Chemother. 44:3444-3446, 2000). A G
184
S mutation adjacent to the serine involved in the binding of
d
-Ala1 in the
d
-alanine:
d
-alanine ligase (Ddl) led to production of an impaired Ddl and accounts for the lack of
d
-alanyl-
d
-alanine-containing peptidoglycan precursors. The sequence of the
vanD
gene cluster revealed eight open reading frames. The organization of this operon, assigned to a chromosomal location, was similar to those in other VanD type strains. The distal part encoded the VanH
D
dehydrogenase, the VanD ligase, and the VanX
D
dipeptidase, which were homologous to the corresponding proteins in VanD-type strains. Upstream from the structural genes for these proteins was the
vanY
D
gene; a frameshift mutation in this gene resulted in premature termination of the encoded protein and accounted for the lack of penicillin-susceptible
d
,
d
-carboxypeptidase activity. Analysis of the translated sequence downstream from the stop codon, but in a different reading frame because of the frameshift mutation, indicated homology with penicillin binding proteins (PBPs) with a high degree of identity with VanY
D
from VanD-type strains. The 5′ end of the gene cluster contained the
vanR
D
-vanS
D
genes for a putative two-component regulatory system. Insertion of IS
Efa4
in the
vanS
D
gene led to constitutive expression of vancomycin resistance. This new insertion belonged to the IS
605
family and was composed of two open reading frames encoding putative transposases of two unrelated insertion sequence elements, IS
200
and IS
1341
.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
64 articles.
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