PMID:15388450

Citation	Depardieu, F, Kolbert, M, Pruul, H, Bell, J and Courvalin, P (2004) VanD-type vancomycin-resistant Enterococcus faecium and Enterococcus faecalis. Antimicrob. Agents Chemother. 48:3892-904
Abstract	Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 microg/ml, respectively) and to low levels of teicoplanin (4 microg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 microg/ml) and susceptible to teicoplanin (0.25 microg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d-alanyl-d-lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX(D) activity, which is not required in the absence of d-Ala-d-Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY(D) activity in the membrane fractions was inhibited by penicillin G. The mutations E(13)G in the region of d-alanine:d-alanine ligase (which is implicated in d-Ala1 binding in A902) and S(319)N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d-Ala-d-Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS(D) of BM4539 and BM4540 and a 1-bp deletion in vanS(D) of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS(D), had a G(140)E mutation in VanR(D) that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS(D) or vanR(D) gene that lead to constitutive resistance to vancomycin.
Links	PubMed PMC521886 Online version:10.1128/AAC.48.10.3892-3904.2004
Keywords	Amino Acid Sequence; Bacterial Proteins/genetics; Bacterial Proteins/physiology; Carboxypeptidases/genetics; Chromosomes, Bacterial/genetics; Computer Simulation; DNA Primers; DNA, Bacterial/genetics; Dipeptidases/genetics; Electrophoresis, Gel, Pulsed-Field; Enterococcus faecalis/drug effects; Enterococcus faecalis/genetics; Enterococcus faecalis/growth & development; Enterococcus faecium/drug effects; Enterococcus faecium/genetics; Enterococcus faecium/growth & development; Molecular Sequence Data; Multigene Family/genetics; Peptide Synthases/genetics; Peptide Synthases/physiology; Plasmids/genetics; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic/genetics; Vancomycin Resistance/genetics; Vancomycin Resistance/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
ENTFC:Q9EZQ9		GO:0046677: response to antibiotic	ECO:0000314:		P		Table 2 shows that enterococci with VanD have high minimum inhibitory concentrations (MIC) of vancomycin.	complete CACAO 4913
ENTFC:Q9EZQ9		GO:0016805: dipeptidase activity	ECO:0000314:		F		Table 6 shows the dipeptidase activity of enterococci with VanD.	complete CACAO 4914

References

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