Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human brucellosis can be acquired from infected animal tissues by ingestion, inhalation, or contamination of the conjunctiva or traumatized skin by infected animal products. A vaccine to protect humans from occupational exposure or from zoonotic infection in areas where the disease is endemic would reduce an important cause of morbidity worldwide. Vaccines currently used in animals are unsuitable for human use. We tested a live, attenuated, purine-auxotrophic mutant strain of Brucella melitensis, WR201, for its ability to elicit cellular and humoral immune responses and to protect mice against intranasal challenge with B. melitensis 16M. Mice inoculated intraperitoneally with WR201 made serum antibody to lipopolysaccharide and non-O-polysaccharide antigens. Splenocytes from immunized animals released interleukin-2 (IL-2), gamma interferon, and IL-10 when cultured with Brucella antigens. Immunization led to protection from disseminated infection but had only a slight effect on clearance of the challenge inoculum from the lungs. These studies suggest that WR201 should be further investigated as a vaccine to prevent human brucellosis.
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PMID:Protection of mice against brucellosis by vaccination with Brucella melitensis WR201(16MDeltapurEK). 1053 Dec 43

The live attenuated Brucella abortus strain RB51 is a rifampin-resistant, lipopolysaccharide (LPS) O-chain-deficient mutant of virulent B. abortus 2308. The reduced O-chain content in RB51 prevents this bacterium from inducing antibodies detectable by the conventional serologic tests for bovine brucellosis diagnosis that mainly identify antibodies to LPS. The absence of available serologic tests for RB51 also complicates the diagnosis of possible RB51 infections in humans exposed to this strain. The purpose of this study was to evaluate the suitability of a complement fixation (CF) test performed with the rough strain B. abortus RB51, previously deprived of anticomplementary activity, in detecting anti-B. abortus RB51 antibodies in cattle and sheep experimentally vaccinated with this strain. The results of this study showed that a CF test with RB51 as the antigen is able to specifically detect antibodies following RB51 vaccination in cattle and sheep. In addition, this method could be a useful tool for detecting B. abortus RB51 infection in humans.
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PMID:Complement fixation test to assess humoral immunity in cattle and sheep vaccinated with Brucella abortus RB51. 1054 64

The lipopolysaccharide (LPS) is up to now the only identified major virulence determinant of Brucella. This bacterium is responsible for brucellosis in animals and for Malta fever in humans. Several monoclonal antibodies (mAbs) directed against various LPS epitopes have been characterized. Two mAbs, named A15-6B3 and B66-2C8, directed against distinct LPS epitopes have been used to select peptides from 11 phage display libraries. The sequences of the selected peptides contain an overrepresentation of either proline or tryptophan residues when selected with either A15-6B3 or B66-2C8 mAbs, respectively. For the best binding peptides, competition with LPS for the binding to the mAb is detected, which suggests that the peptides bind to the paratope of the mAb. The phages selected from the libraries were used to immunise mice, and a weak antibody response directed against LPS has been observed. These data suggest that a subset of the selected peptides are mimotopes of the LPS epitopes.
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PMID:Antigenic properties of peptidic mimics for epitopes of the lipopolysaccharide from Brucella. 1055 37

Entry of opsonized pathogens into phagocytes may benefit or, paradoxically, harm the host. Opsonization may trigger antimicrobial mechanisms such as reactive oxygen or nitric oxide (NO) production but may also provide a safe haven for intracellular replication. Brucellae are natural intramacrophage pathogens of rodents, ruminants, dogs, marine mammals, and humans. We evaluated the role of opsonins in Brucella-macrophage interactions by challenging cultured murine peritoneal macrophages with Brucella melitensis 16M treated with complement- and/or antibody-rich serum. Mouse serum rich in antibody against Brucella lipopolysaccharide (LPS) (aLPS) and human complement-rich serum (HCS) each enhanced the macrophage uptake of brucellae. Combinations of suboptimal levels of aLPS (0. 01%) and HCS (2%) synergistically enhanced uptake. The intracellular fate of ingested bacteria was evaluated with an optimal concentration of gentamicin (2 microg/ml) to control extracellular growth but not kill intracellular bacteria. Bacteria opsonized with aLPS and/or HCS grew equally well inside macrophages in the absence of gamma interferon (IFN-gamma). Macrophage activation with IFN-gamma inhibited replication of both opsonized and nonopsonized brucellae but was less effective in inhibiting replication of nonopsonized bacteria. IFN-gamma treatment of macrophages with opsonized or nonopsonized bacteria enhanced NO production, which was blocked by N(G)-monomethyl L-arginine (MMLA), an NO synthesis inhibitor. MMLA also partially blocked IFN-gamma-mediated bacterial growth inhibition. These studies suggest that primary murine macrophages have limited ability to control infection with B. melitensis, even when activated by IFN-gamma in the presence of highly opsonic concentrations of antibody and complement. Additional cellular immune responses, e.g., those mediated by cytotoxic T cells, may play more important roles in the control of murine brucellosis.
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PMID:Effects of opsonization and gamma interferon on growth of Brucella melitensis 16M in mouse peritoneal macrophages in vitro. 1060 96

Smooth lipopolysaccharide (S-LPS) and lipid A of Brucella abortus and Brucella melitensis induced the production of nitric oxide (NO) by rat adherent peritoneal cells, but they induced lower levels of production of NO than Escherichia coli LPS. The participation of the inducible isoform of NO synthase (iNOS) was confirmed by the finding of an increased expression of both iNOS mRNA and iNOS protein. These observations might help to explain (i) the acute outcome of Brucella infection in rodents, (ii) the low frequency of septic shock in human brucellosis, and (iii) the prolonged intracellular survival of Brucella in humans.
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PMID:Lipopolysaccharides of Brucella abortus and Brucella melitensis induce nitric oxide synthesis in rat peritoneal macrophages. 1067 1

A survey was carried out to verify the sensitivity and specificity of various tests (complement fixation test--CF; agar gel immunodiffusion--AGID; indirect enzyme linked immunosorbent assay--ELISA; immunoblotting--IB) employed in the serological diagnosis of brucellosis caused by Brucella ovis. The tests were executed on 44 blood serum samples of rams coming from B. ovis-free flocks, 75 of B. ovis experimentally infected rams and 1139 from rams living in flocks where B. ovis had been previously isolated. All tests were performed using B. ovis hot saline extract (HS) as antigen. Sensitivity results were 97.4% for IB, 98.68% for CF, 100% for AGID and ELISA; specificity was 100% for all methods. Concordance values were 89.62% (CF-AGID), 78.77% (CF-ELISA), 77.74% (AGID-ELISA), 65.45% (IB-CF), 62.93% (IB-ELISA), 67.24% (IB-AGID). IB identified antibodies to antigenic components with molecular weight of 67, 63, 58, 55, 38, 35, 32, 30, 28, 25, 23, 21, 20-18 kDa (proteins) and 15-12 kDa (rough lipopolysaccharide).
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PMID:Evaluation of tests employed in serological diagnosis of brucellosis caused by Brucella ovis. 1093 43

Genetically based natural resistance to brucellosis in cattle provides for novel strategies to control zoonotic diseases. Bovine NRAMP1, the homologue of a murine gene (Bcg), has been identified as a major candidate for controlling the in vivo resistant phenotype. We developed an in vitro model for expression of resistance- and susceptibility-associated alleles of bovine NRAMP1 as stable transgenes under the regulatory control of the bovine NRAMP1 promoter in the murine RAW264.7 macrophage cell line (Bcg(s)) to analyze the regulation of the NRAMP1 gene and its role in macrophage function. We demonstrated that the 5'-flanking region of bovine NRAMP1, despite the lack of TATA and CAAT boxes, has a functional promoter capable of driving the expression of a transgene in murine macrophages. A polymorphism within a microsatellite in the 3' untranslated region critically affects the expression of bovine NRAMP1 and the control of in vitro replication of Brucella abortus but not Salmonella enterica serovar Dublin. We did not observe any differences in the production of NO by resting or gamma interferon (IFN-gamma)- and IFN-gamma-lipopolysaccharide (LPS)-treated transfected cell lines, yet the resistant transfected cell lines produced significantly less NO than other cell lines, following stimulation with LPS at 24 and 48 h.
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PMID:Stable transfection of the bovine NRAMP1 gene into murine RAW264.7 cells: effect on Brucella abortus survival. 1129 30

Antibodies to cytoplasmic proteins (CP) of Brucella have been shown to be useful for the diagnosis of human brucellosis; however, some early-diagnosed patients lack such an antibody response while having high titers of antibodies to lipopolysaccharide (LPS). To address which factors determine this serological discrepancy in the early stages of brucellosis we examined the antibody response to CP and LPS of 21 patients involved in an outbreak of B. melitensis infection who had a short duration of clinical illness at diagnosis (3-40 d). At diagnosis, antibodies to LPS (IgM and/or IgG) were found in all patients, while anti-CP antibodies were detected in 16 subjects (76%). At 6 weeks post-diagnosis IgG to CP (with or without IgM) had been detected in 13 patients and IgM alone had been found in 4; however, 4 other patients (19%) had no response to CP. No significant differences were found between these 3 groups in terms of age, gender, antimicrobial agents or factors that could hamper the immune response. Notably, however, the 4 non-responders and 3 of the 4 patients having only IgM to CP had started antibiotic therapy within 14 d post-symptoms, while treatment was started later in 9 of 13 patients who developed anti-CP IgG. In addition, maximum titers of IgG to CP tended to be lower in early-treated patients. These results suggest that very early antibiotic therapy hampers the antibody response to Brucella CP but has little impact on the anti-LPS response. Given the higher specificity of the former and the higher sensitivity of the latter, both reactivities should be measured in order to diagnose human brucellosis.
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PMID:Limited diagnostic usefulness of antibodies to cytoplasmic proteins of Brucella in early-treated human brucellosis. 1130 10

The results of a dipstick assay for the detection of immunoglobulin M (IgM) to Brucella smooth lipopolysaccharide (S-LPS) correlated with those of an enzyme-linked immunosorbent assay (ELISA) for IgM and of the serum agglutination test (SAT) performed with and without dithiothreitol. Two sera which were dithiothreitol-sensitive and were dipstick negative were shown to contain specific IgA. The dipstick assay is recommended as a simple method for detecting specific IgM antibodies in acute-phase brucellosis patients.
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PMID:Evaluation of three methods to measure anti-Brucella IgM antibodies and interference of IgA in the interpretation of mercaptan-based tests. 1147 68

The comparison of serological responses in a sample of adult, vaccinated and held-infected bovines with Brucella abortus is reported. Indirect enzyme immunoassav (EIA) titration curves and Western blotting tests for smooth-type lipopolysaccharide (S-LPS), rough-type LPS (R-LPS) and lipid A were performed. In the initial screening of sera, an overall prevalence of 20.5% was found, which corresponds to a country with a high incidence of brucellosis. End-point EIA titres against LPS antigens from vaccinated and field-infected cows were not significantly different. However, the absorbance values in the titration curves were significantly higher for S-LPS as compared with the other antigens. A high correlation coefficient (r = 0.933) was obtained when the titres to R-LPS versus lipid A were compared. Western blotting reactions of vaccinated and held-infected animals were indistinguishable. S-LPS, R-LPS and lipid A epitopes were recognized in a heterogeneous manner. In general, the number of bovines that reacted against LPS was higher in the field-infected group, with a stronger binding to S-LPS. Based on our observations, the vaccinated and field-infected bovines are capable of producing similar antibody responses to the Brucella main outer surface antigen, LPS. It should be emphasized that the humoral response of cattle to Brucella LPS contains significant amounts of antibodies to other antigenic moieties of this important surface molecule, which may contribute to the immunity to brucellosis.
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PMID:Comparison of the antibody response in adult cattle against different epitopes of Brucella abortus lipopolysaccharide. 1170 81


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