Vancomycin resistance VanS/VanR two-component systems.

Vancomycin is a member of the glycopeptide class of antibiotics. Vancomycin resistance (van) gene clusters are found in human pathogens such as Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus, glycopeptide-producing actinomycetes such as Amycolotopsis orientalis, Actinoplanes teichomyceticus and Streptomyces toyocaensis and the nonglycopeptide producing actinomycete Streptomyces coelicolor. Expression of the van genes is activated by the VanS/VanR two-component system in response to extracellular glycopeptide antibiotic. Two major types of inducible vancomycin resistance are found in pathogenic bacteria; VanA strains are resistant to vancomycin itself and also to the lipidated glycopeptide teicoplanin, while VanB strains are resistant to vancomycin but sensitive to teicoplanin. Here we discuss the enzymes the van genes encode, the range of different VanS/VanR two-component systems, the biochemistry of VanS/VanR, the nature of the effector ligand(s) recognised by VanS and the evolution of the van cluster.

[1]  J Davies,et al.  Inactivation of antibiotics and the dissemination of resistance genes. , 1994, Science.

[2]  L. Gutmann,et al.  Synergy and resistance to synergy between beta-lactam antibiotics and glycopeptides against glycopeptide-resistant strains of Enterococcus faecium , 1994, Antimicrobial Agents and Chemotherapy.

[3]  W. Alborn,et al.  Induction of VanA vancomycin resistance genes in Enterococcus faecalis: use of a promoter fusion to evaluate glycopeptide and nonglycopeptide induction signals. , 1997, Microbial drug resistance.

[4]  A. Tomasz,et al.  Penicillin-Binding Protein 2 Is Essential for Expression of High-Level Vancomycin Resistance and Cell Wall Synthesis in Vancomycin- Resistant Staphylococcus aureus Carrying the Enterococcal vanA Gene Complex , 2004, Antimicrobial Agents and Chemotherapy.

[5]  T. Msadek,et al.  A six amino acid deletion, partially overlapping the VanSB G2 ATP‐binding motif, leads to constitutive glycopeptide resistance in VanB‐type Enterococcus faecium , 2003, Molecular microbiology.

[6]  S. Walker,et al.  Vancomycin analogues active against vanA-resistant strains inhibit bacterial transglycosylase without binding substrate , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Zhong Chen,et al.  Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. , 1999, Science.

[8]  C. Walsh,et al.  Vancomycin resistance in enterococci: reprogramming of the D-ala-D-Ala ligases in bacterial peptidoglycan biosynthesis. , 2000, Chemistry & biology.

[9]  C. Walsh,et al.  Characterization of vanY, a DD-carboxypeptidase from vancomycin-resistant Enterococcus faecium BM4147 , 1992, Antimicrobial Agents and Chemotherapy.

[10]  Dudley H. Williams,et al.  Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics , 1995, Antimicrobial agents and chemotherapy.

[11]  A. Tomasz,et al.  High Level Oxacillin and Vancomycin Resistance and Altered Cell Wall Composition in Staphylococcus aureus Carrying the Staphylococcal mecA and the Enterococcal vanA Gene Complex* , 2004, Journal of Biological Chemistry.

[12]  T. Nicas,et al.  Activity of glycopeptides against vancomycin-resistant gram-positive bacteria , 1989, Antimicrobial Agents and Chemotherapy.

[13]  B. Weisblum,et al.  A vancomycin-inducible lacZ reporter system in Bacillus subtilis: induction by antibiotics that inhibit cell wall synthesis and by lysozyme , 1996, Journal of bacteriology.

[14]  A. Kolb,et al.  Binding sites of VanRB and σ70 RNA polymerase in the vanB vancomycin resistance operon of Enterococcus faecium BM4524 , 2005, Molecular microbiology.

[15]  C. Walsh,et al.  Bacterial resistance to vancomycin: five genes and one missing hydrogen bond tell the story. , 1996, Chemistry & biology.

[16]  L. Carrano,et al.  Resistance to Glycopeptide Antibiotics in the Teicoplanin Producer Is Mediated by van Gene Homologue Expression Directing the Synthesis of a Modified Cell Wall Peptidoglycan , 2007, Antimicrobial Agents and Chemotherapy.

[17]  M. Arthur,et al.  Regulation of VanA- and VanB-Type Glycopeptide Resistance in Enterococci , 2001, Antimicrobial Agents and Chemotherapy.

[18]  Ling Li,et al.  The CroRS Two-Component Regulatory System Is Requiredfor Intrinsic β-Lactam Resistance in Enterococcusfaecalis , 2003, Journal of bacteriology.

[19]  C. Walsh,et al.  Assembling the glycopeptide antibiotic scaffold: The biosynthesis of from Streptomyces toyocaensis NRRL15009 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Z. Jiang,et al.  Screening systems for detecting inhibitors of cell wall transglycosylation in Enterococcus. Cell wall transglycosylation inhibitors in Enterococcus. , 1998, The Journal of antibiotics.

[21]  D. Williams,et al.  Binding of glycopeptide antibiotics to a model of a vancomycin-resistant bacterium. , 1999, Chemistry & biology.

[22]  Jeff Pootoolal,et al.  Glycopeptide antibiotic resistance. , 2003, Annual review of pharmacology and toxicology.

[23]  M. Arthur,et al.  Regulated interactions between partner and non-partner sensors and response regulators that control glycopeptide resistance gene expression in enterococci. , 1999, Microbiology.

[24]  L. Gutmann,et al.  Association constants for the binding of vancomycin and teicoplanin to N-acetyl-D-alanyl-D-alanine and N-acetyl-D-alanyl-D-serine. , 1994, The Biochemical journal.

[25]  M. Baptista,et al.  Single‐cell analysis of glycopeptide resistance gene expression in teicoplanin‐resistant mutants of a VanB‐type Enterococcus faecalis , 1999, Molecular microbiology.

[26]  H. Pearson 'Superbug' hurdles key drug barrier , 2002, Nature.

[27]  G. Wright,et al.  Inhibition of sporulation, glycopeptide antibiotic production and resistance in Streptomyces toyocaensis NRRL 15009 by protein kinase inhibitors. , 2001, FEMS microbiology letters.

[28]  C. Walsh,et al.  Identification of the DNA-binding site for the phosphorylated VanR protein required for vancomycin resistance in Enterococcus faecium. , 1994, Biochemistry.

[29]  N. Allen,et al.  Induction of vancomycin resistance in Enterococcus faecium by non-glycopeptide antibiotics. , 1995, FEMS microbiology letters.

[30]  T. Mascher Intramembrane-sensing histidine kinases: a new family of cell envelope stress sensors in Firmicutes bacteria. , 2006, FEMS microbiology letters.

[31]  Lubbert Dijkhuizen,et al.  Organization of the teicoplanin gene cluster in Actinoplanes teichomyceticus. , 2004, Microbiology.

[32]  P. Courvalin,et al.  Vancomycin Resistance in Enterococci Due to Synthesis of Precursors Terminating in d-Alanyl-d-Serine , 2005, Antimicrobial Agents and Chemotherapy.

[33]  M. Buttner,et al.  The vancomycin resistance VanRS two‐component signal transduction system of Streptomyces coelicolor , 2006, Molecular microbiology.

[34]  P. Griffin,et al.  Direct interaction of a vancomycin derivative with bacterial enzymes involved in cell wall biosynthesis. , 2001, Chemistry & biology.

[35]  J. Carbeck,et al.  The Role of Hydrophobic Substituents in the Biological Activityof Glycopeptide Antibiotics , 2000 .

[36]  M. Arthur,et al.  Specificity of induction of glycopeptide resistance genes in Enterococcus faecalis , 1996, Antimicrobial agents and chemotherapy.

[37]  E. Guittet,et al.  Modification of peptidoglycan precursors is a common feature of the low-level vancomycin-resistant VANB-type Enterococcus D366 and of the naturally glycopeptide-resistant species Lactobacillus casei, Pediococcus pentosaceus, Leuconostoc mesenteroides, and Enterococcus gallinarum , 1994, Journal of bacteriology.

[38]  Dudley H. Williams,et al.  Detailed binding sites of the antibiotics vancomycin and ristocetin A: determination of intermolecular distances in antibiotic/substrate complexes by use of the time-dependent NOE , 1983 .

[39]  G. Wright,et al.  Characterization of an inducible vancomycin resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug resistance , 2004, Molecular microbiology.

[40]  C. Walsh,et al.  Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. , 1991, Biochemistry.

[41]  M. Baptista,et al.  Mutations leading to increased levels of resistance to glycopeptide antibiotics in VanB‐type enterococci , 1997, Molecular microbiology.

[42]  S. Handwerger,et al.  Induction of vancomycin resistance in Enterococcus faecium by inhibition of transglycosylation. , 1990, FEMS microbiology letters.

[43]  M. Arthur,et al.  Requirement of the VanY and VanX D,D‐peptidases for glycopeptide resistance in enterococci , 1998, Molecular microbiology.

[44]  C. Walsh,et al.  Transcriptional regulation of the Enterococcus faecium BM4147 vancomycin resistance gene cluster by the VanS-VanR two-component regulatory system in Escherichia coli K-12 , 1997, Journal of bacteriology.

[45]  M. Buttner,et al.  The Role of the Novel Fem Protein VanK in Vancomycin Resistance in Streptomyces coelicolor* , 2005, Journal of Biological Chemistry.

[46]  D. Williams,et al.  The structure and mode of action of glycopeptide antibiotics of the vancomycin group. , 1984, Annual review of microbiology.

[47]  S. McAllister,et al.  Vancomycin-Resistant Staphylococcus aureus Isolate from a Patient in Pennsylvania , 2004, Antimicrobial Agents and Chemotherapy.

[48]  D. Kirsch,et al.  Induction signals for vancomycin resistance encoded by the vanA gene cluster in Enterococcus faecium , 1996, Antimicrobial agents and chemotherapy.

[49]  C. Walsh,et al.  Purification and characterization of VanR and the cytosolic domain of VanS: a two-component regulatory system required for vancomycin resistance in Enterococcus faecium BM4147. , 1993, Biochemistry.

[50]  M. Arthur,et al.  The VanS sensor negatively controls VanR-mediated transcriptional activation of glycopeptide resistance genes of Tn1546 and related elements in the absence of induction , 1997, Journal of bacteriology.

[51]  L. Gutmann,et al.  Peptidoglycan structure of Lactobacillus casei, a species highly resistant to glycopeptide antibiotics , 1997, Journal of bacteriology.

[52]  M. Arthur,et al.  The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin. , 1995, Gene.

[53]  Fred C Tenover,et al.  Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. , 2003, The New England journal of medicine.

[54]  J. Shetty,et al.  Genetic Analysis of a High-Level Vancomycin-Resistant Isolate of Staphylococcus aureus , 2003, Science.

[55]  S. Donadio,et al.  Glycopeptide resistance determinants from the teicoplanin producer Actinoplanes teichomyceticus. , 2004, FEMS microbiology letters.

[56]  Jinping,et al.  Vancomycin-resistant Leuconostoc mesenteroides and Lactobacillus casei synthesize cytoplasmic peptidoglycan precursors that terminate in lactate , 1994, Journal of bacteriology.

[57]  J. Heijenoort Formation of the glycan chains in the synthesis of bacterial peptidoglycan , 2001 .

[58]  Younghoon R. Cho,et al.  The roles of dimerization and membrane anchoring in activity of glycopeptide antibiotics against vancomycin-resistant bacteria , 1997 .

[59]  C. Walsh,et al.  The structural basis for induction of VanB resistance. , 2002, Journal of the American Chemical Society.