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)

To assess the humoral immunological responses at the subclass level in shigellosis, specific antibody responses against Shigella dysenteriae 1 lipopolysaccharide (LPS), S. flexneri Y LPS, invasion plasmid-coded protein antigens (Ipa), and Shiga toxin were analyzed. Antibody responses of 41 patients with S. dysenteriae 1 infection (SDIP) and 15 patients with S. flexneri infection (SFIP) were compared with those of controls (n = 40). The levels of total immunoglobulin G (IgG), IgA, IgM, and albumin in serum and stool samples were analyzed. In addition, total IgA (t-IgA), secretory IgA (s-IgA), and antigen-specific s-IgA in fecal samples were analyzed to evaluate the specificities and magnitudes of the mucosal immune responses. By comparing the relative increases in optical density for each IgG subclass separately, it was determined that the anti-LPS (homologous) response initially increased in the order IgG2 > IgG1 > IgG3 > IgG4 and that this order changed to IgG2 > IgG3 > IgG1 > IgG4 later in the disease. The IgG subclass response against protein antigens initially showed the order IgG1 > IgG3 > IgG2 > IgG4, which changed to IgG3 > IgG1 > IgG2 > IgG4 later in the disease. A significant increase in the proportion of IgA2 among t-IgA compared with that in controls was seen in both SDIP and SFIP, while significant changes in the proportions of IgG1 and IgG2 among t-IgG compared with controls was seen only in SDIP. The anti-LPS IgA2 response was more prominent in SDIP than in SFIP. We found an early peak of antigen-specific s-IgA in fecal samples, with a shorter duration than the corresponding response in serum samples. The simultaneous increase of serum IgA, fecal t-IgA, and s-IgA in SDIP compared with those in SFIP suggests that there is a massive increase in the local IgA production, giving an increase in systemic IgA concomitant with an extensive gut mucosal inflammation leading to an increased loss of albumin, IgG, and IgA with a high ratio of t-IgA to s-IgA.
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PMID:Immunoglobulin subclass distribution and dynamics of Shigella-specific antibody responses in serum and stool samples in shigellosis. 772 20

An approach for studying neurotoxicity of bacterial products is presented. Pentylenetetrazol, a convulsant drug, was injected into mice, and increased sensitivity to pentylenetetrazol was used as an indicator of neurotoxicity. The preinjection of sonicates of Shigella dysenteriae 60R or Escherichia coli H30 (producing Shiga toxin or Shiga-like toxin I, respectively) enhanced the response of mice to pentylenetetrazol within 6 h. This was indicated by a higher mean convulsion score, increased number of mice responding with convulsions, and induction of seizures in animals pretreated with a subepileptic dose of pentylenetetrazol. Preinjection of purified Shiga toxin significantly changed the response to pentylenetetrazol only when coadministered with bacterial lipopolysaccharide (LPS); mean convulsion scores were 1.6 and 0.9 for the Shiga toxin-LPS group and controls, respectively. LPS alone did not affect sensitivity to pentylenetetrazol. These results suggest that Shiga toxin and LPS together induce neurologic disorders early in the course of infection.
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PMID:An animal model for the study of neurotoxicity of bacterial products and application of the model to demonstrate that Shiga toxin and lipopolysaccharide cooperate in inducing neurologic disorders. 775

Eight cases of hemolytic-uremic syndrome in which no pathogens were isolated were diagnosed serologically by a passive hemagglutination assay and a verotoxin (VT; Shiga-like toxin) enzyme-linked immunosorbent assay (ELISA). The passive hemagglutination assay employed formalinized sheep erythrocytes sensitized with soluble native antigen or heat-treated antigen (lipopolysaccharide [LPS]) from Escherichia coli O26, O111, O128, and O157 or flagellar antigen of nine different H serogroups of E. coli: H2, H7, H8, H10, H11, H12, H18, H19, and H25. All patients had antibodies against the native antigen and/or the LPS of E. coli O157, but positive agglutination with H7 was observed only in one patient. In the VT-ELISA with plates coated with purified VT 1 or VT 2, antibody against VT 2 was observed in the sera of five of six patients examined, but none of the patients possessed VT 1 antibody. These results indicate that the causative pathogen in these eight hemolytic-uremic syndrome cases is likely to be VT-producing E. coli O157. The passive hemagglutination assay described here is a very sensitive, simple, and rapid method. This assay is highly recommended for the serological diagnosis of VT-producing E. coli infections, particularly in patients infected by serogroup O157 strains. Furthermore, the VT-ELISA is useful in studying the role of VT in hemolytic-uremic syndrome.
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PMID:Serodiagnosis by passive hemagglutination test and verotoxin enzyme-linked immunosorbent assay of toxin-producing Escherichia coli infections in patients with hemolytic-uremic syndrome. 802 49

Shiga-like-toxin (SLT)-producing Escherichia coli strains, especially serotype O157:H7, are important causes of bloody diarrhea and are associated with the development of hemolytic-uremic syndrome (HUS). Enzyme-linked immunosorbent assays (ELISAs) were developed for the serologic detection of immunoglobulin M (IgM), IgG, and IgA to Shiga toxin (ST) and SLT-I, IgG to SLT-II, and IgM and IgG reactive against E. coli O157 lipopolysaccharide (LPS). Serum samples were collected from 27 HUS patients (25 pediatric and 2 adult) and tested in the ELISAs. Of 27 patients, 10 (37%) were positive for at least one class of antibody to ST/SLT-I. None of the patients were positive for IgG antibody to SLT-II. Twenty-one of the 27 patients (78%) were positive for antibody to E. coli O157 LPS; 19 of 27 (70%) were positive for IgM, and 20 of 27 (74%) were positive for IgG. None of 48 control serum samples were positive in any of the toxin assays, and only 1 of 48 (2%) and 2 of 48 (4%) were positive for IgM and IgG, respectively, to E. coli O157 LPS. Twelve of the 24 patients (50%) from whom stool specimens were collected were positive by culture for E. coli O157. Overall, serology and culture produced confirmation of infection by SLT-producing organisms in 23 of 27 (85%) HUS patients. A combination of ELISA for antibodies to E. coli O157 LPS and culture provided evidence for 22 of 27 (82%) of these patients. The results indicate that while ELISAs for ST/SLT-I and SLT-II antibodies were of limited diagnostic value, the ELISAs for IgM and IgG to E. coli O157 LPS provided valuable and sensitive adjuncts to culture.
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PMID:Humoral immune responses to Shiga-like toxins and Escherichia coli O157 lipopolysaccharide in hemolytic-uremic syndrome patients and healthy subjects. 805 Dec 41

Renal glomerular microvascular endothelial cell damage is characteristic of Shiga toxin-associated hemolytic uremic syndrome (HUS). An impaired renal fibrinolysis may be responsible for renal microvascular fibrin accumulation during the course of HUS disease. This study examined the effect of Shiga toxin, bacterial lipopolysaccharide (LPS, endotoxin), and tumor necrosis factor (TNF) on the expression of fibrinolysis factors by human renal glomerular microvascular endothelial cells (HRMEC) in vitro. The results were compared to a previously better-characterized endothelial cell type, human umbilical vein endothelial cells (HUVEC). In HUVEC, the ratio of fibrinolysis antigens was antifibrinolytic, consisting of 55-fold more plasminogen activator inhibitor type 1 (PAI-1) than tissue-type plasminogen activator (tPA). Treatment of HUVEC with LPS or TNF accentuated this ratio by decreasing tPA and increasing PAI-1 expression. In contrast, HRMEC produced urokinase-type plasminogen activator (uPA) in a 24-fold excess to PAI-1 and were thereby profibrinolytic with regard to fibrinolysis antigen expression. LPS and TNF further decreased PAI-1 antigen expression by HRMEC. These results argue against a role for LPS or TNF in decreasing renal fibrinolysis at the level of fibrinolysis factor expression by renal endothelial cells. Nevertheless, HUVEC and HRMEC were responsive to the same LPS analogs in the same order of potency. Shiga toxin decreased fibrinolysis factor expression to a greater extent in HRMEC than in HUVEC. Since HRMEC fibrinolysis antigen expression was profibrinolytic, the Shiga toxin-mediated decrease in renal endothelial uPA synthesis may predispose renal microvasculature to thrombosis and may have implications for the development of HUS.
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PMID:Human renal microvascular endothelial cells as a potential target in the development of the hemolytic uremic syndrome as related to fibrinolysis factor expression, in vitro. 808 1

This study addresses the basis for regional microvascular susceptibility to bacterial toxins implicated in hemolytic uremic syndrome. The results indicate a relationship between the degree of Shiga toxin sensitivity of human endothelial cells from different sources and the amount of globotriaosylceramide (Gb3) glycosphingolipid receptor for Shiga toxin expressed by these cells. Cell viability and protein synthesis of renal endothelial cells were reduced to 50% by 1 pM Shiga toxin, while umbilical vein cells were not affected by > 1 nM toxin. Similarly, basal levels of Gb3 were approximately 50 times higher in renal endothelial cells than in the umbilical endothelial cells. Pre-exposure of umbilical endothelial cells to tumor necrosis factor-alpha or bacterial lipopolysaccharide increased Gb3 content 4-6-fold coincident with increases in sensitivity to cytotoxic and protein synthesis inhibitory effects of Shiga toxin. Lipopolysaccharide induction of both Gb3 and sensitivity to Shiga toxin cytotoxic action in umbilical endothelial cells was dependent on the structure of lipopolysaccharide. Neither tumor necrosis factor-alpha nor lipopolysaccharide altered the Shiga toxin sensitivity or the Gb3 content of renal endothelial cells. These data indicate that differential endothelial expression of glycolipid receptors for Shiga toxins may be responsible for localized involvement of the kidney in hemolytic uremic syndrome.
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PMID:Endothelial heterogeneity in Shiga toxin receptors and responses. 834 Mar 76

Four murine monoclonal antibodies (MAbs) reactive with the outer-core region of the lipopolysaccharide (LPS) from Haemophilus influenzae were generated after immunization with azide-killed H. influenzae RM.7004 AH1-2 and their epitope specificities studied. The monoclonal antibodies: MAHI 6 (IgM), MAHI 5 (IgG2a), MAHI 8 (IgG3), and MAHI 11 (IgG2b) bound to synthetic glycoconjugates or glycolipids with terminal galabiosyl (Gal alpha 1-->4Gal beta 1-) or globotriaosyl (Gal alpha 1-->4Gal beta 1 1-->4GLc) residues as evaluated in enzyme immunoassays (EIA). Glycoconjugates or glycolipids with internally placed galabiose elements were not active, indicating selectively of the MAbs for recognition of the epitope. Nine LPSs from H. influenzae inhibited the binding of the four MAbs. The presence of the galabiosyl disaccharide element in these nine LPSs was evidence by the binding of 125I-labeled Shiga toxin isolated from the bacterium Shigella dysenteriae type 1, reported to have as receptor the Gal alpha 1-->4Gal beta disaccharide (Lindberg et al., J Biol Chem, 1987, 262: 1779-85). Structural studies of these H. influenzae LPSs were also in accord with the presence of the galabiosyl disaccharide, in addition 1H-NMR spectroscopy showed the presence of O-acetyl groups in the RM.7004 AH1-2 LPS. However, differential binding specificities of the MAbs to modified RM.7004 AH1-2 LPSs were observed. MAHI 6 and MAHI 11 bound equally well to LPS, polysaccharides obtained after mild acidic treatment, and dephosphorylated LPS samples as shown in inhibition EIA. In contrast, both dephosphorylated LPS samples and polysaccharides were poorer inhibitors of the binding of MAHI 5 and MAHI 8 to native RM.7004 AH1-2 LPS. Neither the de-O-acylated nor the de-O,N-acylated LPSs were effective inhibitors of any of the four MAbs. These results suggest that the MAbs recognition involves Gal alpha 1-->4Gal and O-acetyl and other saccharide residue(s) from the oligosaccharide moiety of the LPS. The epitopes are also expressed and accessible to recognition in clinical isolates coming from different sources of Neisseria spp., Haemophilus spp., and Moraxella catarrhalis, but not in Bordetella spp., Aeromonas spp. or Enterobacteriaceae as evaluated by whole-bacteria EIA and colony-dot-immunoblotting.
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PMID:Binding specificity for four monoclonal antibodies recognizing terminal Gal alpha 1-->4Gal residues in Haemophilus influenzae lipopolysaccharide. 855 43

To examine the reported heterogeneity of endothelial cells to Shiga-like toxin 1 (Stx1), the responses of human umbilical (HUVEC) and saphenous (HSVEC) vein endothelial cells to cytokines, butyrate, and toxin were compared. Untreated HSVEC were generally more susceptible than were HUVEC to Stx1; pretreatment of either cell with lipopolysaccharide, interleukin-1 beta, or tumor necrosis factor-alpha enhanced Stx1 toxicity. Dexamethasone alone increased total globotriaosylceramide (Gb3) content and toxin binding but inhibited cytokine-enhanced cytotoxicity, whereas the differentiation agent, sodium butyrate, increased both Gb3 content and cytotoxicity responses to Stx1, most prominently in HSVEC. Stx1 toxicity directly correlated with the release of von Willebrand factor from HSVEC but not from HUVEC. Thus, HUVEC and HSVEC exhibit distinctive responses to Stx1, cytokines, and butyrate. This suggests the need for caution in extrapolating from in vitro studies utilizing one endothelial cell type to in vivo events during pathogenesis of Stx-mediated thrombotic microangiopathies.
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PMID:Comparison of the effects of Shiga-like toxin 1 on cytokine- and butyrate-treated human umbilical and saphenous vein endothelial cells. 862 68

Host mediators play an important role in the pathogenesis of shigellosis and Shiga toxin toxicity. Nitric oxide (NO) production in mouse peritoneal macrophages and in the macrophage J744 cell line in response to purified Shiga toxin and lipopolysaccharide (LPS) from Shigella flexneri were studied. Shiga toxin induced NO production in a dose-dependent manner up to 800 ng/ml. Detectable levels of NO were present as early as 4 h after induction and continued to increase during 72 h; Shiga toxin induced greater NO production with time than did LPS. Pre-treatment of Shiga toxin (400 ng/ml) or LPS (10 ng/ml) with polymyxin B, which inactivates LPS, reduced their ability to induce NO by 28% and 96%, respectively. Induction in the presence of anti-TNF alpha antibodies did not reduce the amount of NO in the supernate. These studies showed that Shiga toxin induces NO production in murine macrophages.
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PMID:Induction of nitric oxide production in mouse macrophages by Shiga toxin. 868 58

Shiga-toxigenic Escherichia coli strains belonging to serotype O157 are important human pathogens, but the genetic basis of expression of the O157 antigen and the role played by the lipopolysaccharide O side chain in the adherence of this organism to epithelial cells are not understood. We performed TnphoA mutagenesis on E. coli O157:H7 strain 86-24 to identify a mutant (strain F12) deficient in O-antigen expression. Nucleotide sequence analysis demonstrated that the transposon inserted within an open reading frame with significant homology to rfbE of Vibrio cholerae O1 (U. H. Stroeher, L. E. Karageorgos, R. Morona, and P. A. Manning, Proc. Natl. Acad. Sci. USA 89:2566-2570, 1992), which is postulated to encode perosamine synthetase. This open reading frame was designated rfbE(EcO157:H7). The guanine-plus-cytosine fraction (0.35) suggests that rfbE(EcO157:H7) may have originated in a species other than E. coli. rfbE(EcO157:H7) is conserved in nontoxigenic E. coli O157 strains expressing a variety of other flagellar antigens but is not found in E. coli O55:H7 strains, which are more closely related to E. coli O157:H7. Strain F12 was significantly more adherent to HeLa cells in a quantitative adherence assay than was its E. coli O157:H7 parent, but they did not differ in other phenotypes. Restoration of the expression of the O side chain by complementation of the TnphoA mutation in strain F12 by a plasmid expressing intact rfbE(EcO157:H7) reduced the adherence of the hyperadherent strain F12. We conclude that rfbE(EcO157:H7) is necessary for the expression of the O157 antigen, that acquisition of E. coli rfb genes occurred independently in E. coli O157:H7 and unrelated O157 strains, and that the O side chain of E. coli O157:H7 lipopolysaccharide interferes with the adherence of E. coli O157:H7 to epithelial cells.
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PMID:Role of the Escherichia coli O157:H7 O side chain in adherence and analysis of an rfb locus. 889 Feb 41


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