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The vanG glycopeptide resistance operon from Enterococcus faecalis revisited
Author(s) -
Depardieu Florence,
Bonora Maria Grazia,
Reynolds Peter E.,
Courvalin Patrice
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03737.x
Subject(s) - biology , operon , gene cluster , microbiology and biotechnology , genetics , enterococcus faecalis , gene , frameshift mutation , mutation , mutant , escherichia coli
Summary Acquired VanG‐type resistance to vancomycin (MIC = 16 µg 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 Zn 2+ 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.