The Experts below are selected from a list of 24150 Experts worldwide ranked by ideXlab platform
Keiichi Hiramatsu - One of the best experts on this subject based on the ideXlab platform.
-
Advances in Vancomycin Resistance: Research in Staphylococcus aureus
Frontiers in Antimicrobial Resistance, 2014Co-Authors: Keiichi Hiramatsu, Longzhu Cui, Maria Kapi, Yutaka Tajima, Teruyo Ito, Suwanna TrakulsomboonAbstract:This chapter concentrates on the mechanisms and biological features of Vancomycin Resistance in methicillin- and cephem-resistant Staphylococcus aureus (MRSA). Vancomycin-resistant S. aureus (VRSA) strains isolated from three American patients contained plasmids carrying the vanA gene complex. The gene complex is carried on a transposon which seems to have been transferred by conjugation from Vancomycin-resistant enterococcus (VRE) that coexisted in the patients’ bodies. The enzyme encoded by the vanA gene, together with those encoded by the adjacent genes vanH, vanX, and vanY, replaces D-alanyl-D-alanine residues of S. aureus peptidoglycan by D-alanyl-D-lactate. In the cell wall of Mu50, peptidoglycan crosslinking is significantly decreased as compared to hetero-Vancomycin-intermediate S. aureus (VISA) strain Mu3 or Vancomycin susceptible S. aureus (VSSA) strains. That is, there are more D-alanyl-D-alanine false targets in the cell-wall peptidoglycan layers of Mu50 than in those of control strains. The Vancomycin Resistance of VISA is not due to the acquisition of a Resistance gene from another bacterial species. It is generated spontaneously from VSSA strains in vitro, though the development of the VISA phenotype does not occur through a single-step selection process. A remarkable feature of hetero-VISA is that it can be obtained from the VSSA strain by selection with beta-lactam antibiotics. A high-thoroughput sequencing strategy for regulator genes in combination with microarray transcription profiling in many isogenic VISA and hetero-VISA combinations might reveal several alternative series of regulator mutations.
-
contribution of vrasr and grasr point mutations to Vancomycin Resistance in Vancomycin intermediate staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Longzhu Cui, Hui Min Neoh, Mitsutaka Shoji, Keiichi HiramatsuAbstract:We describe here the genetic analysis of a Vancomycin-susceptible Staphylococcus aureus (VSSA) strain, Mu50Ω, a strain related to Vancomycin-intermediate S. aureus (VISA) strain Mu50. Using a combination of Mu50Ω whole-genome sequencing and genome engineering, we observed a stepwise evolution of Vancomycin Resistance from VSSA to VISA after the mutated vraS and graR genes of Mu50 were engineered into Mu50Ω.
-
correlation between reduced daptomycin susceptibility and Vancomycin Resistance in Vancomycin intermediate staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Longzhu Cui, Eiji Tominaga, Hui Min Neoh, Keiichi HiramatsuAbstract:We present here findings of a strong positive correlation between reduced daptomycin susceptibility and Vancomycin Resistance in Vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with Vancomycin Resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin Resistance in S. aureus.
-
Vancomycin Resistance in staphylococci.
Drug Resistance Updates, 2005Co-Authors: Keiichi HiramatsuAbstract:Recent emergence of Vancomycin Resistance in methicillin-resistant Staphylococcus aureus (VRSA) has posed a new threat to hospital infection control and antibiotic chemotherapy. Relatively low-level Resistance of VRSA compared to that of Vancomycin-resistant enterococci (VRE), and prevalence of S. aureus clinical strains heterogeneously resistant to Vancomycin (hetero-VRSA), challenge the value of routine antibiotic susceptibility tests as a tool for the prediction of clinical efficacy of Vancomycin therapy. This review summarizes the history of emergence of glycopeptide Resistance in staphylococci and considers the mechanism of Resistance in these organisms.
-
cell wall thickening is a common feature of Vancomycin Resistance in staphylococcus aureus
Journal of Clinical Microbiology, 2003Co-Authors: Katsuhiro Sato, Keiko Okuma, Fred C Tenover, Elsa Masae Mamizuka, Curtis G Gemmell, Mariececile Ploy, El N Solh, Vivian Ferraz, Keiichi HiramatsuAbstract:We have previously shown that a thickened cell wall is responsible for the Vancomycin Resistance of Vancomycin-resistant Staphylococcus aureus (VRSA) (equivalent to Vancomycin-intermediate S. aureus and glycopeptide-intermediate S. aureus) strain Mu50 (L. Cui, H. Murakami, K. Kuwahara-Arai, H. Hanaki, and K. Hiramatsu, Antimicrob. Agents Chemother. 44:2276-2285, 2000). However, the mechanism of Vancomycin Resistance in other VRSA strains remained unclear. In this study, 16 clinical VRSA strains from seven countries were subjected to serial daily passage in drug-free medium. After 10 to 84 days of passage in the nonselective medium, passage-derived strains with decreased MICs of Vancomycin (MIC,
Mark J. Buttner - One of the best experts on this subject based on the ideXlab platform.
-
Vancomycin Resistance vans vanr two component systems
Advances in Experimental Medicine and Biology, 2008Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.
-
The Role of the Novel Fem Protein VanK in Vancomycin Resistance in Streptomyces coelicolor
Journal of Biological Chemistry, 2005Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Lionel Hill, Mark J. ButtnerAbstract:The non-pathogenic, non-glycopeptide-producing actinomycete Streptomyces coelicolor carries a cluster of seven genes (vanSRJKHAX) that confers inducible, high level Resistance to Vancomycin. The vanK gene has no counterpart in previously characterized Vancomycin Resistance clusters, yet vanK is required for Vancomycin Resistance in S. coelicolor. VanK belongs to the Fem family of enzymes, which add the branch amino acid(s) to the stem pentapeptide of peptidoglycan precursors. Upon exposure to Vancomycin, the VanRS two-component system switches on expression of all seven van genes, and the VanHAX enzymes reprogram the cell wall such that precursors terminate D-Ala-D-lactate (Lac) rather than D-Ala-D-Ala, thus conferring Resistance to Vancomycin, which only binds D-Ala-D-Ala-containing precursors. Here we provide biochemical and genetic evidence that VanK is required for Vancomycin Resistance because the constitutively expressed FemX enzyme, encoded elsewhere on the chromosome, cannot recognize D-Lac-containing precursors as a substrate, whereas VanK can. Consistent with this view, D-Lac-containing precursors carrying the Gly branch are present in the wild type transiently exposed to Vancomycin but are undetectable in a vanK mutant treated in the same way. Further, femX null mutants are viable in the presence of Vancomycin but die in its absence. Because only VanK can recognize D-Lac-containing precursors, Vancomycin-induced expression of VanHAX in a vanK mutant is lethal, and so vanK is required for Vancomycin Resistance.
-
Characterization of an inducible Vancomycin Resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug Resistance.
Molecular Microbiology, 2004Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Gerard D Wright, John M. Neu, Mark S. B. Paget, Mark J. ButtnerAbstract:Vancomycin is the front-line therapy for treating problematic infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and the spread of Vancomycin Resistance is an acute problem. Vancomycin blocks cross-linking between peptidoglycan intermediates by binding to the d-Ala-d-Ala termini of bacterial cell wall precursors, which are the substrate of transglycosylase/transpeptidase. We have characterized a cluster of seven genes (vanSRJKHAX) in Streptomyces coelicolor that confers inducible, high-level Vancomycin Resistance. vanHAX are orthologous to genes found in Vancomycin-resistant enterococci that encode enzymes predicted to reprogramme peptidoglycan biosynthesis such that cell wall precursors terminate in d-Ala-d-Lac rather than d-Ala-d-Ala. vanR and vanS encode a two-component signal transduction system that mediates transcriptional induction of the seven van genes. vanJ and vanK are novel genes that have no counterpart in previously characterized Vancomycin Resistance clusters from pathogens. VanK is a member of the Fem family of enzymes that add the cross-bridge amino acids to the stem pentapeptide of cell wall precursors, and vanK is essential for Vancomycin Resistance. The van genes are organized into four transcription units, vanRS, vanJ, vanK and vanHAX, and these transcripts are induced by Vancomycin in a vanR-dependent manner. To develop a sensitive bioassay for inducers of the Vancomycin Resistance system, the promoter of vanJ was fused to a reporter gene conferring Resistance to kanamycin. All the inducers identified were glycopeptide antibiotics, but teicoplanin, a membrane-anchored glycopeptide, failed to act as an inducer. Analysis of mutants defective in the vanRS and cseBC cell envelope signal transduction systems revealed significant cross-talk between the two pathways.
-
Vancomycin Resistance VanS/VanR Two-Component Systems
Advances in Experimental Medicine and Biology, 1Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.
Hee-jeon Hong - One of the best experts on this subject based on the ideXlab platform.
-
Vancomycin Resistance vans vanr two component systems
Advances in Experimental Medicine and Biology, 2008Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.
-
The Role of the Novel Fem Protein VanK in Vancomycin Resistance in Streptomyces coelicolor
Journal of Biological Chemistry, 2005Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Lionel Hill, Mark J. ButtnerAbstract:The non-pathogenic, non-glycopeptide-producing actinomycete Streptomyces coelicolor carries a cluster of seven genes (vanSRJKHAX) that confers inducible, high level Resistance to Vancomycin. The vanK gene has no counterpart in previously characterized Vancomycin Resistance clusters, yet vanK is required for Vancomycin Resistance in S. coelicolor. VanK belongs to the Fem family of enzymes, which add the branch amino acid(s) to the stem pentapeptide of peptidoglycan precursors. Upon exposure to Vancomycin, the VanRS two-component system switches on expression of all seven van genes, and the VanHAX enzymes reprogram the cell wall such that precursors terminate D-Ala-D-lactate (Lac) rather than D-Ala-D-Ala, thus conferring Resistance to Vancomycin, which only binds D-Ala-D-Ala-containing precursors. Here we provide biochemical and genetic evidence that VanK is required for Vancomycin Resistance because the constitutively expressed FemX enzyme, encoded elsewhere on the chromosome, cannot recognize D-Lac-containing precursors as a substrate, whereas VanK can. Consistent with this view, D-Lac-containing precursors carrying the Gly branch are present in the wild type transiently exposed to Vancomycin but are undetectable in a vanK mutant treated in the same way. Further, femX null mutants are viable in the presence of Vancomycin but die in its absence. Because only VanK can recognize D-Lac-containing precursors, Vancomycin-induced expression of VanHAX in a vanK mutant is lethal, and so vanK is required for Vancomycin Resistance.
-
Characterization of an inducible Vancomycin Resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug Resistance.
Molecular Microbiology, 2004Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Gerard D Wright, John M. Neu, Mark S. B. Paget, Mark J. ButtnerAbstract:Vancomycin is the front-line therapy for treating problematic infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and the spread of Vancomycin Resistance is an acute problem. Vancomycin blocks cross-linking between peptidoglycan intermediates by binding to the d-Ala-d-Ala termini of bacterial cell wall precursors, which are the substrate of transglycosylase/transpeptidase. We have characterized a cluster of seven genes (vanSRJKHAX) in Streptomyces coelicolor that confers inducible, high-level Vancomycin Resistance. vanHAX are orthologous to genes found in Vancomycin-resistant enterococci that encode enzymes predicted to reprogramme peptidoglycan biosynthesis such that cell wall precursors terminate in d-Ala-d-Lac rather than d-Ala-d-Ala. vanR and vanS encode a two-component signal transduction system that mediates transcriptional induction of the seven van genes. vanJ and vanK are novel genes that have no counterpart in previously characterized Vancomycin Resistance clusters from pathogens. VanK is a member of the Fem family of enzymes that add the cross-bridge amino acids to the stem pentapeptide of cell wall precursors, and vanK is essential for Vancomycin Resistance. The van genes are organized into four transcription units, vanRS, vanJ, vanK and vanHAX, and these transcripts are induced by Vancomycin in a vanR-dependent manner. To develop a sensitive bioassay for inducers of the Vancomycin Resistance system, the promoter of vanJ was fused to a reporter gene conferring Resistance to kanamycin. All the inducers identified were glycopeptide antibiotics, but teicoplanin, a membrane-anchored glycopeptide, failed to act as an inducer. Analysis of mutants defective in the vanRS and cseBC cell envelope signal transduction systems revealed significant cross-talk between the two pathways.
-
Vancomycin Resistance VanS/VanR Two-Component Systems
Advances in Experimental Medicine and Biology, 1Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.
Longzhu Cui - One of the best experts on this subject based on the ideXlab platform.
-
Advances in Vancomycin Resistance: Research in Staphylococcus aureus
Frontiers in Antimicrobial Resistance, 2014Co-Authors: Keiichi Hiramatsu, Longzhu Cui, Maria Kapi, Yutaka Tajima, Teruyo Ito, Suwanna TrakulsomboonAbstract:This chapter concentrates on the mechanisms and biological features of Vancomycin Resistance in methicillin- and cephem-resistant Staphylococcus aureus (MRSA). Vancomycin-resistant S. aureus (VRSA) strains isolated from three American patients contained plasmids carrying the vanA gene complex. The gene complex is carried on a transposon which seems to have been transferred by conjugation from Vancomycin-resistant enterococcus (VRE) that coexisted in the patients’ bodies. The enzyme encoded by the vanA gene, together with those encoded by the adjacent genes vanH, vanX, and vanY, replaces D-alanyl-D-alanine residues of S. aureus peptidoglycan by D-alanyl-D-lactate. In the cell wall of Mu50, peptidoglycan crosslinking is significantly decreased as compared to hetero-Vancomycin-intermediate S. aureus (VISA) strain Mu3 or Vancomycin susceptible S. aureus (VSSA) strains. That is, there are more D-alanyl-D-alanine false targets in the cell-wall peptidoglycan layers of Mu50 than in those of control strains. The Vancomycin Resistance of VISA is not due to the acquisition of a Resistance gene from another bacterial species. It is generated spontaneously from VSSA strains in vitro, though the development of the VISA phenotype does not occur through a single-step selection process. A remarkable feature of hetero-VISA is that it can be obtained from the VSSA strain by selection with beta-lactam antibiotics. A high-thoroughput sequencing strategy for regulator genes in combination with microarray transcription profiling in many isogenic VISA and hetero-VISA combinations might reveal several alternative series of regulator mutations.
-
contribution of vrasr and grasr point mutations to Vancomycin Resistance in Vancomycin intermediate staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2009Co-Authors: Longzhu Cui, Hui Min Neoh, Mitsutaka Shoji, Keiichi HiramatsuAbstract:We describe here the genetic analysis of a Vancomycin-susceptible Staphylococcus aureus (VSSA) strain, Mu50Ω, a strain related to Vancomycin-intermediate S. aureus (VISA) strain Mu50. Using a combination of Mu50Ω whole-genome sequencing and genome engineering, we observed a stepwise evolution of Vancomycin Resistance from VSSA to VISA after the mutated vraS and graR genes of Mu50 were engineered into Mu50Ω.
-
correlation between reduced daptomycin susceptibility and Vancomycin Resistance in Vancomycin intermediate staphylococcus aureus
Antimicrobial Agents and Chemotherapy, 2006Co-Authors: Longzhu Cui, Eiji Tominaga, Hui Min Neoh, Keiichi HiramatsuAbstract:We present here findings of a strong positive correlation between reduced daptomycin susceptibility and Vancomycin Resistance in Vancomycin-intermediate Staphylococcus aureus (VISA). This correlation is related to cell wall thickening, suggesting that, similar to the case with Vancomycin Resistance in VISA, the physical barrier of a thickened cell wall may contribute to daptomycin Resistance in S. aureus.
Matthew I. Hutchings - One of the best experts on this subject based on the ideXlab platform.
-
Vancomycin Resistance vans vanr two component systems
Advances in Experimental Medicine and Biology, 2008Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.
-
The Role of the Novel Fem Protein VanK in Vancomycin Resistance in Streptomyces coelicolor
Journal of Biological Chemistry, 2005Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Lionel Hill, Mark J. ButtnerAbstract:The non-pathogenic, non-glycopeptide-producing actinomycete Streptomyces coelicolor carries a cluster of seven genes (vanSRJKHAX) that confers inducible, high level Resistance to Vancomycin. The vanK gene has no counterpart in previously characterized Vancomycin Resistance clusters, yet vanK is required for Vancomycin Resistance in S. coelicolor. VanK belongs to the Fem family of enzymes, which add the branch amino acid(s) to the stem pentapeptide of peptidoglycan precursors. Upon exposure to Vancomycin, the VanRS two-component system switches on expression of all seven van genes, and the VanHAX enzymes reprogram the cell wall such that precursors terminate D-Ala-D-lactate (Lac) rather than D-Ala-D-Ala, thus conferring Resistance to Vancomycin, which only binds D-Ala-D-Ala-containing precursors. Here we provide biochemical and genetic evidence that VanK is required for Vancomycin Resistance because the constitutively expressed FemX enzyme, encoded elsewhere on the chromosome, cannot recognize D-Lac-containing precursors as a substrate, whereas VanK can. Consistent with this view, D-Lac-containing precursors carrying the Gly branch are present in the wild type transiently exposed to Vancomycin but are undetectable in a vanK mutant treated in the same way. Further, femX null mutants are viable in the presence of Vancomycin but die in its absence. Because only VanK can recognize D-Lac-containing precursors, Vancomycin-induced expression of VanHAX in a vanK mutant is lethal, and so vanK is required for Vancomycin Resistance.
-
Characterization of an inducible Vancomycin Resistance system in Streptomyces coelicolor reveals a novel gene (vanK) required for drug Resistance.
Molecular Microbiology, 2004Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Gerard D Wright, John M. Neu, Mark S. B. Paget, Mark J. ButtnerAbstract:Vancomycin is the front-line therapy for treating problematic infections caused by methicillin-resistant Staphylococcus aureus (MRSA), and the spread of Vancomycin Resistance is an acute problem. Vancomycin blocks cross-linking between peptidoglycan intermediates by binding to the d-Ala-d-Ala termini of bacterial cell wall precursors, which are the substrate of transglycosylase/transpeptidase. We have characterized a cluster of seven genes (vanSRJKHAX) in Streptomyces coelicolor that confers inducible, high-level Vancomycin Resistance. vanHAX are orthologous to genes found in Vancomycin-resistant enterococci that encode enzymes predicted to reprogramme peptidoglycan biosynthesis such that cell wall precursors terminate in d-Ala-d-Lac rather than d-Ala-d-Ala. vanR and vanS encode a two-component signal transduction system that mediates transcriptional induction of the seven van genes. vanJ and vanK are novel genes that have no counterpart in previously characterized Vancomycin Resistance clusters from pathogens. VanK is a member of the Fem family of enzymes that add the cross-bridge amino acids to the stem pentapeptide of cell wall precursors, and vanK is essential for Vancomycin Resistance. The van genes are organized into four transcription units, vanRS, vanJ, vanK and vanHAX, and these transcripts are induced by Vancomycin in a vanR-dependent manner. To develop a sensitive bioassay for inducers of the Vancomycin Resistance system, the promoter of vanJ was fused to a reporter gene conferring Resistance to kanamycin. All the inducers identified were glycopeptide antibiotics, but teicoplanin, a membrane-anchored glycopeptide, failed to act as an inducer. Analysis of mutants defective in the vanRS and cseBC cell envelope signal transduction systems revealed significant cross-talk between the two pathways.
-
Vancomycin Resistance VanS/VanR Two-Component Systems
Advances in Experimental Medicine and Biology, 1Co-Authors: Hee-jeon Hong, Matthew I. Hutchings, Mark J. ButtnerAbstract: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.