KEGG   PATHWAY: vau01502Help
Entry
vau01502                    Pathway                                

Name
Vancomycin resistance - Vibrio anguillarum NB10
Description
Vancomycin (VCM) is a glycopeptide antibiotic agent that inhibits the synthesis of peptidolgycan in the production of bacterial cell walls. It is active in most Gram-positive bacteria and acts by binding to the D-Ala-D-Ala C-terminus of pentapeptide, thus blocking the addition of subunits to the peptidoglycan backbone. The resistance to VCM was first described among enterococci in the late 1980s in Europe. Subsequently, vancomycin-resistant enteococci (VRE) have been observed in many countries. The genes encoding resistance are carried on plasmids that can tranfer themselves from cell to cell and on tranponsons that can jump from plamids to the chromosome. Up to now, at least six resistance operon types are characterized, namely VanA, VanB, VanC, VanD, VanE and VanG. The VanA and VanB operons are detected on plasmids or in the chromosome, whereas the rest are found in the chromosome. In addition, Streptomyces, which is non-pathogenic, non-glycopeptide-producing actinomycete, also shows high-level resistance to VCM. In Streptomyces, novel genes (vanK and vanJ) are characterized with no counterparts found in the resistance clusters of pathogenic bacteria.
The expression of vancomycin resistance pathway is induced by the VanS-VanR two component system, and D-Ala-D-Lac or D-Ala-D-Ser dipsipeptides are formed in place of D-Ala-D-Ala dipeptide. Thus, VCM cannot bind to pentadepsipeptide[D-Lac] or pentadepsipeptide[D-Ser]. The D-Ala-D-Lac variation shows high levels of resistance to VCM, especially in VanA type, wheras the D-Ala-D-Ser variation shows low levels of resistance. The modified pepidoglycan can interact with cross-linking enzymes (PBPs), thus cell wall is successfully formed.
Class
Human Diseases; Drug resistance: antimicrobial
BRITE hierarchy
Pathway map
vau01502  Vancomycin resistance
vau01502

Ortholog table
Organism
Vibrio anguillarum NB10 [GN:vau]
Reference
  Authors
Courvalin P
  Title
Vancomycin resistance in gram-positive cocci.
  Journal
Clin Infect Dis 42 Suppl 1:S25-34 (2006)
DOI:10.1086/491711
Reference
  Authors
Chancey ST, Zahner D, Stephens DS
  Title
Acquired inducible antimicrobial resistance in Gram-positive bacteria.
  Journal
Future Microbiol 7:959-78 (2012)
DOI:10.2217/fmb.12.63
Reference
PMID:8899966
  Authors
Arthur M, Reynolds P, Courvalin P
  Title
Glycopeptide resistance in enterococci.
  Journal
Trends Microbiol 4:401-7 (1996)
DOI:10.1016/0966-842X(96)10063-9
Reference
  Authors
Cetinkaya Y, Falk P, Mayhall CG
  Title
Vancomycin-resistant enterococci.
  Journal
Clin Microbiol Rev 13:686-707 (2000)
DOI:10.1128/CMR.13.4.686-707.2000
Reference
PMID:7854121
  Authors
Reynolds PE, Depardieu F, Dutka-Malen S, Arthur M, Courvalin P
  Title
Glycopeptide resistance mediated by enterococcal transposon Tn1546 requires production of VanX for hydrolysis of D-alanyl-D-alanine.
  Journal
Mol Microbiol 13:1065-70 (1994)
DOI:10.1111/j.1365-2958.1994.tb00497.x
Reference
PMID:8631706
  Authors
Evers S, Courvalin P
  Title
Regulation of VanB-type vancomycin resistance gene expression by the VanS(B)-VanR (B) two-component regulatory system in Enterococcus faecalis V583.
  Journal
J Bacteriol 178:1302-9 (1996)
DOI:10.1128/JB.178.5.1302-1309.1996
Reference
  Authors
Reynolds PE, Arias CA, Courvalin P
  Title
Gene vanXYC encodes D,D -dipeptidase (VanX) and D,D-carboxypeptidase (VanY) activities in vancomycin-resistant Enterococcus gallinarum BM4174.
  Journal
Mol Microbiol 34:341-9 (1999)
DOI:10.1046/j.1365-2958.1999.01604.x
Reference
  Authors
Podmore AH, Reynolds PE
  Title
Purification and characterization of VanXY(C), a D,D-dipeptidase/D,D-carboxypeptidase in vancomycin-resistant Enterococcus gallinarum BM4174.
  Journal
Eur J Biochem 269:2740-6 (2002)
DOI:10.1046/j.1432-1033.2002.02946.x
Reference
  Authors
Reynolds PE, Courvalin P
  Title
Vancomycin resistance in enterococci due to synthesis of precursors terminating in D-alanyl-D-serine.
  Journal
Antimicrob Agents Chemother 49:21-5 (2005)
DOI:10.1128/AAC.49.1.21-25.2005
Reference
  Authors
Arias CA, Weisner J, Blackburn JM, Reynolds PE
  Title
Serine and alanine racemase activities of VanT: a protein necessary for vancomycin resistance in Enterococcus gallinarum BM4174.
  Journal
Microbiology 146 ( Pt 7):1727-34 (2000)
DOI:10.1099/00221287-146-7-1727
Reference
  Authors
Hong HJ, Hutchings MI, Buttner MJ
  Title
Vancomycin resistance VanS/VanR two-component systems.
  Journal
Adv Exp Med Biol 631:200-13 (2008)
DOI:10.1007/978-0-387-78885-2_14
Reference
  Authors
Depardieu F, Bonora MG, Reynolds PE, Courvalin P
  Title
The vanG glycopeptide resistance operon from Enterococcus faecalis revisited.
  Journal
Mol Microbiol 50:931-48 (2003)
DOI:10.1046/j.1365-2958.2003.03737.x
Reference
  Authors
McKessar SJ, Berry AM, Bell JM, Turnidge JD, Paton JC
  Title
Genetic characterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis.
  Journal
Antimicrob Agents Chemother 44:3224-8 (2000)
DOI:10.1128/AAC.44.11.3224-3228.2000
Reference
  Authors
Kwun MJ, Novotna G, Hesketh AR, Hill L, Hong HJ
  Title
In vivo studies suggest that induction of VanS-dependent vancomycin resistance requires binding of the drug to D-Ala-D-Ala termini in the peptidoglycan cell wall.
  Journal
Antimicrob Agents Chemother 57:4470-80 (2013)
DOI:10.1128/AAC.00523-13
Reference
  Authors
Hong HJ, Hutchings MI, Neu JM, Wright GD, Paget MS, Buttner MJ
  Title
Characterization of an inducible vancomycin resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug resistance.
  Journal
Mol Microbiol 52:1107-21 (2004)
DOI:10.1111/j.1365-2958.2004.04032.x
Reference
  Authors
Hong HJ, Hutchings MI, Hill LM, Buttner MJ
  Title
The role of the novel Fem protein VanK in vancomycin resistance in Streptomyces coelicolor.
  Journal
J Biol Chem 280:13055-61 (2005)
DOI:10.1074/jbc.M413801200
Reference
  Authors
Hutchings MI, Hong HJ, Buttner MJ
  Title
The vancomycin resistance VanRS two-component signal transduction system of Streptomyces coelicolor.
  Journal
Mol Microbiol 59:923-35 (2006)
DOI:10.1111/j.1365-2958.2005.04953.x
Reference
  Authors
Hesketh A, Hill C, Mokhtar J, Novotna G, Tran N, Bibb M, Hong HJ
  Title
Genome-wide dynamics of a bacterial response to antibiotics that target the cell envelope.
  Journal
BMC Genomics 12:226 (2011)
DOI:10.1186/1471-2164-12-226
Reference
  Authors
Koteva K, Hong HJ, Wang XD, Nazi I, Hughes D, Naldrett MJ, Buttner MJ, Wright GD
  Title
A vancomycin photoprobe identifies the histidine kinase VanSsc as a vancomycin receptor.
  Journal
Nat Chem Biol 6:327-9 (2010)
DOI:10.1038/nchembio.350
Related
pathway
vau00550  Peptidoglycan biosynthesis
KO pathway
ko01502   
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