UNIPROT:P43026 - FACTA Search

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Query: UNIPROT:P43026 (lipopolysaccharide)
62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the secretory immune response after Shigella infection, the anti-lipopolysaccharide and anti-Shiga-toxin response in saliva, obtained from children with confirmed shigellosis and healthy children, were determined by enzyme-linked immunosorbent assay and by Western blot. Children with infection showed high titers compared to healthy controls. After Shigella dysenteriae type 1 infection a significant change in titer could be observed in a large number of cases, in contrast to Shigella flexneri infection. It appeared that, in children living in endemic areas, infection with one serotype can give a rise in antibody titer to another serotype. This could be ascribed to polyclonal B cell activation since children in endemic areas routinely show relatively high titers to Shigella antigens. We conclude that the dynamics of salivary anti-Shigella LPS and anti-Shiga-toxin in children with dysentery indicate that it can be applied to studies of immune response in shigellosis for epidemiological and vaccination purposes.
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PMID:Shigella-specific IgA in saliva of children with bacillary dysentery. 154 24

The aromatic-dependent live Shigella flexneri Y strain SFL114, attenuated by a Tn10-inactivated aroD gene, was given as an oral vaccine to 14 Macaca fascicularis monkeys. A significant clinical attenuation of SFL114 was seen (p = 0.0058) as all vaccinated monkeys tolerated 2 x 10(10)-1 x 10(11) bacteria of SFL114, whereas four out of seven monkeys orally given 1 x 10(11) of the virulent parent strain SFL1 developed shigellosis. The average excretion time for SFL114 and SFL1 were 2 and 18 days, respectively. As seen endoscopically SFL1 caused colonic lesions, whereas SFL114 did not. Histopathologic examination of colonic biopsies showed that SFL114 induced only slight acute inflammation, whereas SFL1 caused severe acute inflammation (p less than 0.01). The vaccine strain SFL114 elicited significant species-specific serum immune responses (p less than 0.005) as seen in enzyme immune assays using lipopolysaccharides from S. flexneri serotypes Y, 1b, and 2a and Escherichia coli K-12 as antigens. The titres were comparable to those seen in monkeys given virulent S. flexneri strains. Western blot analyses showed that many prevaccination sera contained antibodies directed against the invasion plasmid-coded polypeptides. However, after vaccination with SFL114 increased amounts of such anti-polypeptide antibodies were seen, particularly in sera from monkeys having a low prevaccination antibody level. SFL114 also elicited a significant species-specific (p less than 0.025) local intestinal sIgA response against the homologous lipopolysaccharide antigen. Vaccinated monkeys were clinically protected against an oral challenge with 1-2 x 10(11) live, virulent S. flexneri strains of any of serotypes Y (strain SFL1), 1b (strain SFL27), or 2a (strain M4243).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Auxotrophic live oral Shigella flexneri vaccine protects monkeys against challenge with S. flexneri of different serotypes. 155 32

A live, oral Shigella vaccine, constructed by transfer of the 140-MDa invasiveness plasmid from Shigella flexneri 5 and the chromosomal genes encoding the group- and type-specific O antigen of S. flexneri 2a to Escherichia coli K-12, was tested in humans. Designated EcSf2a-1, this vaccine produced adverse reactions (fever, diarrhea, or dysentery) in 4 (31%) of 13 subjects who ingested a single dose of 1.0 x 10(9) CFU, while at better-tolerated doses (5.0 x 10(6) to 5.0 x 10(7) CFU), it provided no significant protection against challenge with S. flexneri 2a. A further-attenuated aroD mutant derivative, EcSf2a-2, was then tested. Rhesus monkeys that received EcSf2a-2 in three oral doses of ca. 1.5 x 10(11) CFU experienced no increase in gastrointestinal symptoms compared with a control group that received an E. coli K-12 placebo. Compared with controls, the vaccinated monkeys were protected against shigellosis after challenge with S. flexneri 2a (60% efficacy; P = 0.001). In humans, EcSf2a-2 was well tolerated at inocula ranging from 5.0 x 10(6) to 2.1 x 10(9) CFU. However, after a single dose of 2.5 x 10(9) CFU, 4 (17%) of 23 subjects experienced adverse reactions, including fever (3 subjects) and diarrhea (209 ml) (1 subject), and after a single dose of 1.8 x 10(10) CFU, 2 of 4 subjects developed dysentery. Recipients of three doses of 1.2 to 2.5 x 10(9) CFU had significant rises in serum antibody to lipopolysaccharide (61%) and invasiveness plasmid antigens (44%) and in gut-derived immunoglobulin A antibody-secreting cells specific for lipopolysaccharide (100%) and invasiveness plasmid antigens (60%). Despite its immunogenicity, the vaccine conferred only 36% protection against illness (fever, diarrhea, or dysentery) induced by experimental challenge (P = 0.17). These findings illustrate the use of an epithelial cell-invasive E. coli strain as a carrier for Shigella antigens. Future studies must explore dosing regimens that might optimize the protective effects of the vaccine while eliminating adverse clinical reactions.
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PMID:Safety, immunogenicity, and efficacy in monkeys and humans of invasive Escherichia coli K-12 hybrid vaccine candidates expressing Shigella flexneri 2a somatic antigen. 158 89

Shigella flexneri SFL124, with a deletion encompassing all, or nearly all, of the coding sequence of gene aroD was obtained after selection on a fusaric acid medium supplemented with 2,3-dihydroxybenzoic acid for tetracycline-sensitive mutants of S. flexneri SFL114 which is an aroD::Tn10 transductant. Two of 20 tetracycline-sensitive mutants tested in colony hybridization with a 32P-labelled DNA probe of approximately 1400 base pairs (comprising all except the 75 N-terminal base pairs of the coding region of gene aroD) did not hybridize. The selected mutant SFL124 is Congo-red positive, invades and shows a limited multiplication in HeLa cells and does not cause keratoconjunctivitis in guinea-pigs. It is well tolerated by Macaca fascicularis monkeys, is excreted for up to 4 days, elicits a slight inflammatory reaction in the colonic mucosa, stimulates significant secretory IgA responses in the intestine and serum IgA and IgG responses against the S. flexneri cell envelope lipopolysaccharide. The immune response conferred a complete protection against challenge with 1 x 10(11) (equivalent to a 100 LD50 dose) live S. flexneri SFL1.
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PMID:Live oral auxotrophic Shigella flexneri SFL124 vaccine with a deleted aroD gene: characterization and monkey protection studies. 159 87

The live, aromatic dependent Shigella flexneri Y vaccine strain SFL124, with a deleted aroD gene, was tested for safety and immunogenicity in 21 healthy adult volunteers. A single dose of 2 x 10(9) live bacteria was given orally to ten volunteers, whereas 11 received three doses every other day. The vaccine was excreted for 4.2 days and was well tolerated by 90.5% of the vaccinees. Only 2 of 21 (9.5%) after the first dose had a self-limiting diarrhoea lasting 1 day; of volunteers given one dose only 3 of 10 showed anti-lipopolysaccharide (LPS) and anti-invasion plasmid coded antigen (Ipa) responses in serum. A faecal antibody response to LPS and Ipa was seen in six and three persons, respectively. Volunteers given three doses reacted with serum anti-LPS (9/11) and anti-Ipa (5/11) antibody responses. In stool, anti-LPS and anti-Ipa responses were detected in nine and eight volunteers, respectively. A booster dose of 2 x 10(9) bacteria given to six volunteers in the three-dose group 9-10 months later elicited high stool sIgA responses, indicating a strong mucosal memory, and was accompanied by a short excretion period of SFL124 (1.8 versus 4.2 days, p less than 0.05). The vaccination also elicited antibody-secreting cell (ASC) responses against LPS in peripheral blood: the three doses of the vaccine resulted in a stronger response than did the single dose, while the booster dose elicited only a limited ASC response. Volunteers previously exposed to shigellae exhibited stronger anti-Ipa responses in serum and stool suggestive of an immunological memory to the Ipa. The results indicate that SFL124 is a safe live vaccine strain inducing specific immune responses against LPS and Ipa with a mucosal immune memory lasting for at least 9 months.
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PMID:Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in volunteers. 159 88

Shigella species have virulence plasmids that encode outer membrane proteins (invasion plasmid antigens, Ipa) associated with pathogenicity. Western blots were used to detect antibodies to Ipa in sera from 390 Chilean children, and these responses were compared with those of a US population of infants and adults. Antibodies to lipopolysaccharide (LPS) of Plesiomonas shigelloides and Shigella flexneri 2a were measured by ELISA. Among the Chileans, there was an age-related acquisition of Ipa antibodies, with 28% of 1-year-olds and 100% of children greater than or equal to 10 years showing positive responses. In contrast, none of the US infants and only 38% of the adults had antibodies to Ipa. Levels of LPS antibodies were also found to increase in an age-related manner among the Chileans. These results corroborate findings of previous epidemiologic studies which show that Shigella infections are endemic in Chile, as in other developing countries. The measurement of Ipa and LPS antibodies is a useful seroepidemiologic tool for investigating previous exposure to Shigella species in populations.
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PMID:Age-specific prevalence of serum antibodies to the invasion plasmid and lipopolysaccharide antigens of Shigella species in Chilean and North American populations. 160 90

Acute- and convalescent-phase sera from 18 Thai patients and convalescent-phase sera from two Israeli patients and one Bangladeshi patient with Shigella dysenteriae 1 (Shiga) dysentery were tested by enzyme-linked immunosorbent assay to detect antibodies that bind S. dysenteriae lipopolysaccharide (LPS), Shiga holotoxin, or two synthetic peptides representing epitopes from the B subunit of Shiga toxin. Paired sera from 24 Maryland adults with Shigella flexneri 2a or Shigella sonnei diarrhea served as negative controls. Of the 16 paired Thai serum samples tested for immunoglobulin G LPS antibody, 10 had greater than or equal to 4-fold rises (the two subjects with the highest convalescent-phase titers exhibited toxin-neutralizing activity); acute-phase specimens from four of the remaining six individuals already had elevated Shiga LPS titers in their acute specimens ranging from 1:800 to 1:12,800. Similarly, convalescent-phase sera from the two Israeli patients and the Bangladeshi patient revealed LPS titers of 1:800 to 1:3,200. In contrast, none of the Maryland volunteers with S. flexneri or S. sonnei diarrhea manifested rises in Shiga anti-LPS (P less than 0.00001 versus 10 of 16 Thai patients). Only 4 of the 18 Thai patients had significant rise in antibody to purified Shiga toxin, while one of the two Israeli patients and the one Bangladeshi patient had elevated convalescent-phase titers. None of the sera that reacted with Shiga holotoxin had antibody that bound to the peptides. This report, which describes a search for serum antibodies that bind Shiga toxin in patients with Shiga dysentery, demonstrates such antibodies in only a minority of patients with bacteriologically confirmed disease. During Shiga dysentery, Shiga toxin may be elaborated in such small quantities in vivo that it fails to elicit an immune response in most patients even though it may exert biological effects. In this behavior Shiga toxin resembles tetanus toxin, another potent exotoxin that fails to elicit antitoxic responses in people who recover from clinical tetanus.
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PMID:Antibodies to shiga holotoxin and to two synthetic peptides of the B subunit in sera of patients with Shigella dysenteriae 1 dysentery. 162 17

To establish the molecular basis of the chromosomal virulence genes of Shigella flexneri 2a (YSH6000), a Notl restriction map of the chromosome was constructed by exploiting Notl-linking clones, partial Notl digestion and DNA probes from various genes of Escherichia coli K-12. The map revealed at least three local differences in the placements of genes between YSH6000 and E. coli K-12. Using the additional Notl sites introduced by Tn5 insertion, nine virulence loci identified previously by random Tn5 insertions were physically mapped on the chromosome. To demonstrate the versatility of the Notl map in direct assignment of the virulence loci tagged by Tn5 to a known genetic region in E. coli K-12, the major class of avirulent mutants defective in the core structure of lipopolysaccharide (LPS) was examined for the sites of Tn5 insertions. The two Notl segments created by the Tn5 insertion in the Notl fragment were analysed by Southern blotting with two DNA probes for the 5' and 3' flanking regions of the rfa region, and shown to hybridize separately with each of them, confirming the sites of Tn5 in the rfa locus. This approach will facilitate direct comparison genetically mapped Tn5 insertion mutations of S. flexneri with genes physically determined in E. coli K-12.
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PMID:Construction of a physical map of the chromosome of Shigella flexneri 2a and the direct assignment of nine virulence-associated loci identified by Tn5 insertions. 166 62

Lysogens of Shigella flexneri harbouring the temperate bacteriophage, Sf6, have been previously shown to undergo a serotype conversion due to O-acetylation of the O-antigen of the lipopolysaccharide. A partial physical map of the phage genome has been constructed. Analysis of the phage DNA suggests that the phage packages by a headful mechanism and that the mature DNA molecules are terminally redundant. Cloning of the PstI fragments of Sf6 enabled the region encoding the serotype conversion to be localized, showing that this was clearly phage-encoded. The gene was further localized by mutagenesis with Tn5 and the nucleotide sequence of the entire 2693-bp PstI fragment was determined. Two major open reading frames (ORFs) were found capable of encoding proteins of 44.1 and 37.2 kDa. The latter corresponds to the O-antigen acetylase and its gene has been designated oac. The oac gene is capable of converting Sh. flexneri serotypes X, Y, 1a and 4a to 3a, 3b, 1b and 4b, respectively. The Oac protein bears a high degree of homology to the NodX protein of Rhizobium leguminosarum suggesting that it, too, may be a sugar acetylase. The second ORF immediately upstream from oac corresponds to the bacteriophage Sf6 integrase responsible for chromosomal integration and is highly homologous to the integrases of Escherichia coli bacteriophages P4 and phi 80, but less closely related to those of P1, P2, P22, 186 and lambda.
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PMID:The oac gene encoding a lipopolysaccharide O-antigen acetylase maps adjacent to the integrase-encoding gene on the genome of Shigella flexneri bacteriophage Sf6. 172 Jul 55

The gene cluster (rfb region) which determines the biosynthesis of the Shigella flexneri O-antigen of the Y serotype specificity was cloned from a S. flexneri serotype 2a strain. Two plasmids, pPM2212 and pPM2213, which conferred O-antigen biosynthesis were generated from separate cosmid clones by deletion with Clal. These plasmids expressed O-antigen in Escherichia coli K12 like that of the parental strain, as assessed by reactions to antisera in colony and Western immunoblots, sensitivity to bacteriophage Sf6, and by silver staining of lipopolysaccharides separated by sodium dodecyl sulphate/polyacrylamide gel electrophoresis. These plasmids also mediated O-antigen expression in an E. coli K12 rfb-delete background, indicating that all the necessary genes have been cloned. A detailed restriction map of the region has been constructed and analysis of various subclones has allowed the limits of the coding region for O-antigen biosynthesis to be defined to a maximum of 11 kb. Expression of these plasmids demonstrates a novel phenotype associated with control of lipopolysaccharide chain length. The gene(s) responsible maps adjacent to, but separate from, those associated with the biosynthesis of the O-antigen unit. Analysis of plasmid-encoded proteins in minicells and maxicells has facilitated the construction of a physical map. Finally, plasmid pPM-2212 was used to probe a collection of S. flexneri serotypes by Southern hybridization. With the exception of serotype 6, which appears to be unrelated, a similar pattern was found in all serotypes.
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PMID:Genetic analysis of the rfb region of Shigella flexneri encoding the Y serotype O-antigen specificity. 172 58

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