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)

Members of the bacterial genus Chlamydia are responsible for widespread disease among humans and animals, including endemic trachoma in developing countries, venereal disease in developed countries, and a variety of other diseases such as infantile pneumonia and lymphogranuloma venereum. Although there is little genetic relatedness between and large antigenic diversity between and among the two chlamydial species, one antigenic determinant has been preserved among all serovars: the genus-specific lipopolysaccharide epitope. In this report, the tools of molecular genetics, monoclonal antibodies, and analytical and synthetic chemistry have been combined to determine the structure of this epitope. This epitope is attributed to the presence of a trisaccharide of 3-deoxy-D-manno-octulosonic acid (KDO) of the sequence KDOp-(2----8)-KDOp-(2----4)-KDO. The structure includes a unique linkage of two KDO residues through a 2.8-linkage.
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PMID:Chemical and serological investigations on the genus-specific lipopolysaccharide epitope of Chlamydia. 243 32

The cell surfaces of two Chlamydia trachomatis serovars were explored by immune electron microscopy with monoclonal antibodies that recognize a number of chlamydial outer-membrane components. Species, subspecies and serovar-reactive epitopes on the major outer-membrane protein (MOMP) of a lymphogranuloma venereum biovar strain, L2/434/Bu, and a trachoma biovar strain, F/UW-6/Cx, were exposed on the surfaces of both elementary bodies (EBs) and reticulate bodies (RBs). Three epitopes on MOMP were inaccessible on EBs and RBs of both strains. These included a genus-reactive, species-reactive, and a subspecies-reactive epitope. In contrast, genus-specific epitopes on lipopolysaccharide (LPS) were not detected on the EB surface, but were clearly expressed on RBs of both L2/434/Bu and F/UW-6/Cx chlamydiae. Antibodies specific for the 60 kDa and 12 kDa 'cysteine-rich' outer-membrane proteins did not react with surface epitopes on either EBs or RBs. These data provide evidence that MOMP is a major surface antigen of both morphological forms, whereas some portions of the LPS molecule are exposed on the RB surface but become inaccessible to antibody after conversion to the infectious EB form.
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PMID:Detection of surface-exposed epitopes on Chlamydia trachomatis by immune electron microscopy. 247 26

The obligate intracellular prokaryote Chlamydia trachomatis is the etiological agent of trachoma and is a primary causative pathogen of sexually transmitted genital tract disease; both diseases affect millions of people each year. The cloning of genes encoding the enzyme or enzymes producing the genus-specific lipopolysaccharide antigen of Chlamydia into Escherichia coli is reported here. The cloned chlamydial lipopolysaccharide antigen appears to be a hybrid lipopolysaccharide molecule composed of both Chlamydia and Escherichia coli components. The chlamydial lipopolysaccharide antigen is expressed on the surfaces of the viable Escherichia coli recombinants. These findings may have a significant impact on defining the role of this highly conserved antigen in the pathogenesis and diagnosis of chlamydial infections.
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PMID:Expression of the chlamydial genus-specific lipopolysaccharide epitope in Escherichia coli. 258 15

Human diseases caused by the intracellular bacterium Chlamydia trachomatis include genital tract infections and blinding trachoma. Chlamydial infections are characterized by chronic inflammation and scarring, and development of such complications is thought to be immunologically mediated. In this study, we show that coculture of C. trachomatis (serovar L2) with human blood monocytes induced the production of interleukin-1 (IL-1), an important mediator of inflammation, tissue remodeling, and scarring. IL-1 was produced in response to UV-inactivated elementary bodies containing from 0.1 to 50 micrograms of protein per ml, with a maximal response at 5 to 10 micrograms/ml. IL-1 activity was detected by 6 h of incubation and was maximal by 24 h. Peak levels were maintained throughout 96 h of incubation. Rabbit antibody to human IL-1(alpha + beta) effectively neutralized the thymocyte-stimulating activity of the supernatants. The apparent molecular weight of chlamydia-induced IL-1 was 16,000, as determined by gel filtration on a Bio-Gel P-60 column. Isoelectric focusing yielded two peaks of activity, with pIs of 5.5 and 6.9. Neutralization studies with antisera against human IL-1 alpha and IL-1 beta showed that the acidic and neutral peaks corresponded to IL-1 alpha and IL-1 beta, respectively, with IL-1 beta predominating. Heat-killed chlamydiae, which are not internalized by monocytes, were effective IL-1 inducers, indicating that phagocytosis was not required for IL-1 induction. Purified C. trachomatis lipopolysaccharide was also an effective IL-1 inducer, suggesting that the response to intact organisms may be largely a response to chlamydial lipopolysaccharide. Finally, purified chlamydial major outer membrane protein induced low but detectable IL-1 activity.
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PMID:Chlamydia trachomatis-induced production of interleukin-1 by human monocytes. 278 36

We have investigated the ability of both species of chlamydiae (C. trachomatis and C. psittaci), two major biovars of C. trachomatis (lymphogranuloma venereum and trachoma), and the two developmental forms of chlamydia (reticulate and elementary bodies) to stimulate murine spleen lymphocytes. All of these forms of the bacteria induce potent proliferation and differentiation to plaque-forming cells by B lymphocytes in vitro. Chlamydiae induce a broad antibody response, suggesting that stimulation is polyclonal in nature. Although all chlamydiae possess a lipopolysaccharide (LPS) genus-specific molecule similar to LPS found on Re mutant enterobacteria, polyclonal B cell stimulation is likely caused by molecules other than LPS, since i) polymyxin B failed to inhibit chlamydia-induced immunostimulation and ii) C3H/HeJ mice (LPS nonresponders) produced normal numbers of PFC after culture with chlamydia (but not LPS). Thus, a cross-species moiety that is not LPS is responsible for polyclonal stimulation by chlamydia. Because these bacteria can exist in latent forms in an animal, and all forms are immunostimulatory, the question of whether these bacteria can alter immune responses if released during other infections or immunizations has been raised.
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PMID:Both species of chlamydia and two biovars of Chlamydia trachomatis stimulate mouse B lymphocytes. 351 67

A panel of monoclonal antibodies (MAb) was generated against Chlamydia trachomatis serovar B, an etiologic agent of blinding trachoma. The specificities of MAb were determined by dot blot assay by using viable elementary bodies of 13 C. trachomatis serovars and two C. psittaci strains. The dot blot assay was used to identify those antigens that were unique and immunoaccessible on the chlamydial surface. MAb were identified that recognized bi-specific (serovars B and Ba) or subspecies-specific (various B complex serovars) surface-exposed antigenic determinants that were either resistant or sensitive to heat denaturation (56 degrees C, 30 min). All of the MAb recognized the major outer membrane protein as determined by either immunoblotting or radioimmunoprecipitation. MAb specific for immunoaccessible major outer membrane protein epitopes protected mice from toxic death after i.v. injection of B serovar elementary bodies and neutralized the infectivity of the organism for monkey eyes. In contrast, MAb reactive against non-immunoaccessible subspecies- or species-specific major outer membrane protein epitopes or against an immunoaccessible genus-specific epitope located on chlamydial lipopolysaccharide did not protect mice from toxic death or neutralize infectivity of the parasite for monkey eyes. These data suggest that those major outer membrane protein antigenic determinants that are serovar or serogroup specific and are accessible to antibody on the chlamydial cell surface may be useful as a recombinant subunit vaccine for trachoma.
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PMID:Protective monoclonal antibodies recognize epitopes located on the major outer membrane protein of Chlamydia trachomatis. 354 Jan 22

Active trachoma is characterized by chronic inflammation of the conjunctiva, and repeated episodes of reinfection are thought to be necessary to sustain this inflammation. It is currently believed that much of the tissue damage is immunologically mediated. To identify which antigens might be responsible for stimulating this continued inflammation, cynomolgus monkeys that had recovered from a previous ocular infection with Chlamydia trachomatis were challenged with various antigen preparations. Purified preparations of formalin- or UV-inactivated elementary bodies did not elicit any inflammation even with daily inoculation. In addition, neither purified chlamydial major outer membrane protein nor lipopolysaccharide, including recombinant organisms expressing the lipopolysaccharide group antigen, elicit inflammation. A soluble triton extract of the organism rapidly induced marked inflammation when inoculated in the eyes of immune monkeys but had no effect in naive animals. These studies suggest that the continual inflammation in trachoma may not be due to repeated exposure to chlamydial surface antigen(s) but rather to a labile product released by the living organisms.
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PMID:Pathogenesis of trachoma: the stimulus for inflammation. 357 82

The gene gseA, involved in the expression of the genus-specific epitope of chlamydial lipopolysaccharide (LPS), was analyzed by temperature gradient gel electrophoresis (TGGE) to visualize nucleotide sequence variations among the 15 serovars of Chlamydia trachomatis. Sequence analysis showed that the TGGE melting-profile patterns were able to detect single nucleotide variations within gseA and allowed the arrangement of the serovars in groups of both identical nucleotide sequences and sequences containing identical sites of nucleotide substitutions. Compared to serovar L2, four types of patterns were obtained: (i) serotypes A and Ba; (ii) B and C (causing endemic trachoma); (iii) D through K (causing sexually transmitted oculo-genital infections); (iv) L1 through L3 (the causative agents of lymphogranuloma venereum). A total of 58 isolated of C. trachomatis of genital or conjunctival origin were tested by this method in comparison to reference strains. Forty-eight isolates (13 of type E, 16 of type F, nine of type G, and ten of type K) yielded the same melting profile as the corresponding type strain, independent of whether they were isolated from genital or ocular infections. However, ten B serotype strains of genital origin behaved in TGGE like a typical genital strain and not a trachoma strain. Thus, although gseA was found to be highly conserved among C. trachomatis, the obtained TGGE profiles of the tested strains tended to correlate with their specific site of infection.
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PMID:Nucleotide sequence variations within the lipopolysaccharide biosynthesis gene gseA (Kdo transferase) among the Chlamydia trachomatis serovars. 786 60

The propensity of two Chlamydia trachomatis strains (L2/434/Bu [biovar LGV] and E/DK20/ON [biovar trachoma]) to induce putative host defense responses upon infection of McCoy (mouse) cell cultures was examined. Both strains induced production of alpha/beta interferon and nitric oxide (NO) by McCoy cells. NO synthesis was mediated by the inducible isoform of NO synthase as indicated by the ability of cycloheximide or the arginine analog NG-monomethyl-L-arginine to abolish NO production; the extent of the response was dependent upon the dose of chlamydiae applied. Incubation of McCoy cells with chloramphenicol prior to infection reduced NO production by strain 434 but not by DK20, suggesting that initial chlamydial metabolism was essential to induction by the LGV strain. Antibody inhibition studies indicated that NO synthesis was dependent upon production of alpha/beta interferon and induction via lipopolysaccharide. Overall, our findings show that chlamydiae are capable of the induction of interferon and NO in murine fibroblasts in the absence of exogenous cytokines. However, the role of NO as an antichlamydial effector could not be clearly demonstrated since treatment with an arginine analog, while suppressing NO production, gave no consistent enhancement of infected cell numbers.
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PMID:Induction of alpha/beta interferon and dependent nitric oxide synthesis during Chlamydia trachomatis infection of McCoy cells in the absence of exogenous cytokine. 892 54