Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The earliest humoral response in patients infected with Borrelia burgdorferi, the agent of Lyme disease, is directed against the spirochete's 41-kDa flagellar antigen. In order to map the epitopes recognized on this antigen, 11 overlapping fragments spanning the flagellin gene were cloned by polymerase chain reaction and inserted into an Escherichia coli expression vector which directed their expression as fusion proteins containing glutathione S-transferase at the N terminus and a flagellin fragment at the C terminus. Affinity-purified fusion proteins were assayed for reactivity on Western blots (immunoblots) with sera from patients with late-stage Lyme disease. The same immunodominant domain was bound by sera from 17 of 18 patients. This domain (comprising amino acids 197 to 241) does not share significant homology with other bacterial flagellins and therefore may be useful in serological testing for Lyme disease.
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PMID:Molecular characterization of the humoral response to the 41-kilodalton flagellar antigen of Borrelia burgdorferi, the Lyme disease agent. 189 59

Due to local variation in the antigenicity of the agent of Lyme disease (Borrelia burgdorferi), a vaccine derived from any one isolate of this spirochete may fail to protect against the heterogeneous population of organisms that may be present in an enzootic focus. Accordingly, we determined whether antigenically variable spirochetes delivered by naturally infected ticks, collected from a site where transmission is intense, may fail to infect mice actively immunized with recombinant glutathione transferase outer surface fusion proteins A or B (OspA and OspB). Virtually all mice vaccinated by either immunogen appeared not to become infected, as determined by culture or histopathology of their tissues. We conclude that Osp vaccination of mice effectively prevents infection by the agent of Lyme disease in a simulated natural cycle of transmission.
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PMID:Protection against antigenically variable Borrelia burgdorferi conferred by recombinant vaccines. 834 Jul 64

C3H mice were actively immunized with outer surface protein A (OspA) at different intervals after infection with Borrelia burgdorferi to determine the effect of postexposure vaccination on the course of murine Lyme borreliosis. Mice were vaccinated with an OspA-glutathione transferase fusion protein or glutathione transferase (control) in complete Freund's adjuvant; vaccination was followed by two weekly booster injections in incomplete adjuvant. Two weeks after the final booster injection, organs were cultured for B. burgdorferi (blood, spleen, skin, and bladder) and examined for histopathology (joints and hearts). When vaccination was commenced in the early stages (5 to 14 days) of infection, active immunization with OspA partially cleared spirochetes from the bloodstream but did not eliminate them from other tissues or alter the course of joint or heart disease. Commencement of vaccination at 60 days after infection (at which time joint or heart disease is resolving), however, reduced both the number of mice and individual joints with arthritis, a result suggesting an acceleration of the resolution phase of the disease. Postexposure immunization with OspA may partially alter the course of murine Lyme arthritis but does not eliminate infection.
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PMID:OspA vaccination of mice with established Borrelia burgdorferi infection alters disease but not infection. 850 Aug 91

Antibodies in the sera of patients with human granulocytic ehrlichiosis (HGE) commonly recognize a 44-kDa antigen. We cloned the gene encoding the 44-kDa protein of the agent of HGE (aoHGE) by probing an aoHGE lambda ZAP II genomic DNA expression library with sera from aoHGE-infected mice. The gene, hge-44, is part of a multigene family, with sequence similarity to the Anaplasma marginale msp-2 genes. RNA-PCR studies confirmed that hge-44 is expressed by aoHGE cultured in HL-60 cells and by aoHGE during murine infection. Recombinant HGE-44, expressed and purified as a glutathione transferase fusion protein, was used as the substrate in immunoblots to help diagnose HGE. Antibodies in eight sera from eight patients with HGE and in two sera from two aoHGE-infected mice bound recombinant HGE-44. Antibodies in the sera of healthy individuals or patients with Ehrlichia chaffeensis or Borrelia burgdorferi infection did not recognize HGE-44. We conclude that hge-44 is a member of a multigene family and that hge-44 is expressed and elicits specific antibodies during infection.
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PMID:Cloning of the gene encoding the 44-kilodalton antigen of the agent of human granulocytic ehrlichiosis and characterization of the humoral response. 963 94

Vaccination with outer surface protein A (OspA) of Borrelia burgdorferi prevents subsequent infection and disease in both laboratory animals and humans with high efficacy. OspA-based immunity, however, does not affect established infection due to the loss of OspA expression in the vertebrate host. We show here that repeated passive transfer of mouse and/or rabbit immune sera to recombinant GST-OspC fusion protein resulted in a dose-dependent resolution (1) of fully established arthritis and carditis as well as infection in needle-challenged C.B-17 SCID and (2) of infection in both experimentally and tick-infected BALB/c mice. Unexpectedly, active immunization of disease-susceptible AKR/N mice with GST-OspC only led to prevention but not resolution of disease and infection, in spite of high serum titers of OspC-specific Ab and the expression of ospC in tissue-derived spirochetes. The data suggest that the efficacy of OspC antibody-mediated immunity depends on the immunological history of the recipient and/or environment-dependent regulation of OspC surface expression by spirochetes in vivo. The results encourage further attempts to develop therapeutic vaccination protocols against Lyme disease.
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PMID:Resolution of experimental and tick-borne Borrelia burgdorferi infection in mice by passive, but not active immunization using recombinant OspC. 1009 99

We have previously described the expression cloning of nine Borrelia burgdorferi antigens, using rabbit serum enriched for antibodies specific for infection-associated antigens, and determined that seven of these antigens were associated with infectious B. burgdorferi strain B31. One of these infection-associated antigens encoded a 451-amino-acid putative lipoprotein containing 21 consecutive and invariant 9-amino-acid repeat sequences near the amino terminus that we have designated VraA for virulent strain-associated repetitive antigen A. The vraA locus (designated BBI16 by The Institute for Genomic Research) maps to one of the 28-kb linear plasmids (designated lp28-4) that is not present in noninfectious strain B31 isolates. Subsequent PCR analysis of clonal isolates of B. burgdorferi B31 from infected mouse skin revealed a clone that lacked only lp28-4. Southern blot and Western blot analyses indicated that the lp28-4 and VraA proteins, respectively, were missing from this clone. We have also determined that VraA is a surface-exposed protein based on protease accessibility assays of intact whole cells. Furthermore, vraA expression is modestly derepressed when cells are grown at 37 degrees C relative to cells grown at 32 degrees C, suggesting that VraA is, in part, a temperature-inducible antigen. Homologues cross-reactive to B. burgdorferi B31 VraA, most with different molecular masses, were identified in several B. burgdorferi sensu lato isolates, including B. andersonii, suggesting that the immunogenic epitope(s) present in strain B31 VraA is conserved between Borrelia spp. In protection studies, only 8.3% of mice (1 of 12) immunized with full-length recombinant VraA fused to glutathione S-transferase (GST) were susceptible to infectious challenge with 10(2) B. burgdorferi strain B31, whereas naive mice or mice immunized with GST alone were infected 40% or 63 to 67% (depending on tissues assayed) of the time, respectively. As such, the partial protection elicited by VraA immunization provides an additional testable vaccine candidate to help protect against Lyme borreliosis.
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PMID:VraA (BBI16) protein of Borrelia burgdorferi is a surface-exposed antigen with a repetitive motif that confers partial protection against experimental Lyme borreliosis. 1117 6

Three recombinant antigens of Treponema pallidum Nichols strain were fused with GST, cloned and expressed in Escherichia coli, resulting in high levels of GST-rTp47 and GST-rTp17 expression, and supplementation with arginine tRNA for the AGR codon was needed to obtain GST-rTp15 overexpression. Purified fusion protein yields were 1.9, 1.7 and 5.3 mg/l of cell culture for GST-rTp47, GST-rTp17 and GST-rTp15, respectively. The identities of the antigens obtained were confirmed by automated DNA sequencing using ABI Prism 310 and peptide mapping by Finningan LC/MS. These recombinant antigens were evaluated by immuno-slot blot techniques applied to 137 serum samples from patients with a clinical and laboratory diagnosis of syphilis (61 samples), from healthy blood donors (50 samples), individuals with sexually transmitted disease other than syphilis (3 samples), and from individuals with other spirochetal diseases such as Lyme disease (20 samples) and leptospirosis (3 samples). The assay had sensitivity of 95.1% (95% CI, 86.1 to 98.7%) and a specificity of 94.7% (95% CI, 87.0 to 98.7%); a stronger reactivity was observed with fraction rTp17. The immunoreactivity results showed that fusion recombinant antigens based-immuno-slot blot techniques are suitable for use in diagnostic assays for syphilis.
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PMID:Recombinant antigen-based immuno-slot blot method for serodiagnosis of syphilis. 1526

Ixodes ricinus L. is the principal European vector of Borrelia burgdorferi sensu lato, the causative agent of Lyme borreliosis. Subtractive hybridization was used to isolate tick genes that were induced in whole ticks after blood meals on uninfected and B. burgdorferi-infected guinea pigs. Novel cDNA clones with similarity to cytochrome c oxidase, salivary secreted protein, actin, and a cysteine protease propeptide were induced after a blood meal. Novel cDNA clones with similarity to thioredoxin peroxidases, dolichyl-phosphate beta-glucosyltransferase, glutathione S-transferase, defensin, ML domain-containing protein, and von Willebrand factor were induced after B. burgdorferi infection. Virtual Northern analysis was used to verify that these genes were differentially expressed in ticks after a pathogen-infected blood meal and to detect their tissues of expression. The characterization of genes that are induced after an infected blood meal is essential for gaining an understanding of the molecular mechanisms that underlie vector-pathogen interactions.
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PMID:Differential expression of Ixodes ricinus tick genes induced by blood feeding or Borrelia burgdorferi infection. 1569 Oct 6

In Borrelia burgdorferi-infected C3H-scid mice, antiserum to a differentially expressed, 37-kDa spirochetal outer-surface protein, termed arthritis-related protein (Arp), has been shown to prevent or reduce the severity of arthritis. In this study, we determined the immunoglobulin G (IgG) antibody responses to this spirochetal protein in single serum samples from 124 antibiotic-treated human patients with early or late manifestations of Lyme disease and in serial serum samples from 20 historic, untreated patients who were followed longitudinally from early infection through the period of arthritis. These 20 patients were representative of the spectrum of the severity and duration of Lyme arthritis. Among the 124 antibiotic-treated patients, 53% with culture-proven erythema migrans (EM) had IgG responses to recombinant glutathione S-transferase (GST)-Arp, as did 59% of the patients with facial palsy and 68% of those with Lyme arthritis. In addition, 75 to 80% of the 20 past, untreated patients had reactivity with this protein when EM was present, during initial episodes of joint pain, or during the maximal period of arthritis. There was no association at any of these three time points between GST-Arp antibody levels and the severity of the maximal attack of arthritis or the total duration of arthritis. Thus, after the first several weeks of infection, 60 to 80% of patients had IgG antibody responses to GST-Arp, but this response did not correlate with the severity or duration of Lyme arthritis.
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PMID:Human Lyme arthritis and the immunoglobulin G antibody response to the 37-kilodalton arthritis-related protein of Borrelia burgdorferi. 1584 1

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