The vanG Glycopeptide Resistance Operon From Enterococcus Faecalis Revisited

Mol Microbiol. 2003 Nov;50(3):931-48. doi: 10.1046/j.1365-2958.2003.03737.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Flanking Region
  • 5' Flanking Region
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Carboxypeptidases / genetics
  • DNA Transposable Elements
  • Drug Resistance, Microbial / genetics*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Electrophoresis, Gel, Pulsed-Field
  • Endopeptidases / genetics
  • Enterococcus faecalis / drug effects
  • Enterococcus faecalis / genetics*
  • Gene Expression Regulation, Bacterial
  • Gene Order
  • Membrane Proteins / genetics
  • Methyltransferases / genetics
  • Molecular Sequence Data
  • Multigene Family
  • Operon*
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Peptidoglycan / metabolism
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Serine-Type D-Ala-D-Ala Carboxypeptidase*
  • Transcription, Genetic
  • Vancomycin Resistance / genetics

Substances

  • Bacterial Proteins
  • DNA Transposable Elements
  • Membrane Proteins
  • Peptidoglycan
  • VanG protein, Enterococcus faecalis
  • Methyltransferases
  • rRNA (adenosine-O-2'-)methyltransferase
  • Carboxypeptidases
  • Endopeptidases
  • Peptide Hydrolases
  • Serine-Type D-Ala-D-Ala Carboxypeptidase
  • VanY protein, Bacteria
  • VanX dipeptidase
  • Racemases and Epimerases
  • serine racemase

Associated data

  • GENBANK/AY271781