The vanG glycopeptide resistance operon from Enterococcus faecalis revisited.
Acquired VanG-type resistance to vancomycin (MIC = 16 micro g ml(-1)) but susceptibility to teicoplanin in Enterococcus faecalis BM4518 and WCH9 is due to the inducible synthesis of peptidoglycan precursors ending in d-alanine-d-serine. The vanG cluster, assigned to a chromosomal location, was composed of genes recruited from various van operons. The 3' end encoded VanG, a d-Ala:d-Ser ligase, VanXY(G), a putative bifunctional d,d-peptidase and VanT(G), a serine racemase: VanG and VanT(G) were implicated in the synthesis of d-Ala:d-Ser as in VanC- and VanE-type strains. Upstream from the structural genes for these proteins were vanW(G) with unknown function and vanY(G) containing a frameshift mutation which resulted in premature termination of the encoded protein and accounted for the lack of UDP-MurNAc-tetrapeptide in the cytoplasm. Without the frameshift mutation, VanY(G) had homology with Zn2+ dependent d,d-carboxypeptidases. The 5' end of the gene cluster contained three genes vanU(G), vanR(G) and vanS(G) encoding a putative regulatory system, which were co-transcribed constitutively from the PY(G) promoter, whereas transcription of vanY(G),W(G),G,XY(G),T(G) was inducible and initiated from the P(YG) promoter. Transfer of VanG-type glycopeptide resistance to E. faecalis JH2-2 was associated with the movement, from chromosome to chromosome, of genetic elements of c. 240 kb carrying also ermB-encoded erythromycin resistance. Sequence determination of the flanking regions of the vanG cluster in donor and transconjugants revealed the same 4 bp direct repeats and 22 bp imperfect inverted repeats that delineated the large element.
Depardieu
Florence
F
Unité des Agents Antibactériens, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, Cedex 15, France.
Bonora
Maria Grazia
MG
Reynolds
Peter E
PE
Courvalin
Patrice
P
D024509:3' Flanking Region; D024506:5' Flanking Region; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002268:Carboxypeptidases / Q000235:genetics; D004251:DNA Transposable Elements; D004352:Drug Resistance, Microbial / Q000235:genetics*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D010450:Endopeptidases / Q000235:genetics; D013293:Enterococcus faecalis / Q000187:drug effects / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D023061:Gene Order; D008565:Membrane Proteins / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009876:Operon; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D014158:Transcription, Genetic; D020713:Vancomycin Resistance / Q000235:genetics; D000099300:Serine Racemase
D001426:Bacterial Proteins; D002268:Carboxypeptidases; D004251:DNA Transposable Elements; D010450:Endopeptidases; D008565:Membrane Proteins; D008780:Methyltransferases; D010447:Peptide Hydrolases; D010457:Peptidoglycan; D019998:Racemases and Epimerases; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; D000099300:Serine Racemase; C417270:VanG protein, Enterococcus faecalis; C035181:rRNA (adenosine-O-2'-)methyltransferase; C117912:VanY protein, Bacteria; C091956:VanX dipeptidase