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)

The outcome of the early stages of a neisserial infection is determined by receptor-mediated events that culminate in the attachment and invasion of human mucosal tissues. The factors participating in this process, including pili, opacity proteins (Opa), and perhaps lipopolysaccharide (LPS), are subject to complex genetic controls that allow these factors to be produced in multiple forms. Antigenic variation allows the pathogenic Neisseriae to evade the human immune response, and facilitates their interaction with a variety of different cells and tissues of the human host. One of the major genetic mechanisms causing antigenic variation is transformation, which allows virulence genes to be exchanged and recombined between independent Neisseria strains within multiply infected individuals. A number of other factors, such as IgA protease, alpha-factor, and the meningococcal capsule are also implicated in pathogenesis and render the pathogenic Neisseriae an excellent model for the investigation of bacterial virulence.
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PMID:Pathogenic neisseriae--a model of bacterial virulence and genetic flexibility. 208 68

The early stages of an infection with pathogenic Neisseriae are determined by receptor-mediated events that finally lead to the attachment and invasion of human mucous tissues. The factors participating in this process, the pili, OPA proteins, and perhaps lipopolysaccharide (LPS), are subject to complex genetic changes that enable the pathogens to produce multiple variant forms of these factors. Antigenic variation of the pathogenic Neisseriae permits both, the escape from the human immune response and the interaction with different cells and tissues of the human host. One of the intrinsic mechanisms of antigenic variation, i.e. genetic transformation, allows exchange and recombination of virulence genes between independent Neisseria strains in multiply infected individuals. Factors, such as IgA protease, alpha-factor, and the meningococcal capsule are attributed with further striking properties, and thus render the pathogenic Neisseriae as an excellent model for the investigation of bacterial virulence.
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PMID:[Pathogenic neisseriae--model of bacterial virulence and genetic flexibility]. 257 Jul 47

Haemophilus influenzae are small, gram-negative, rod-shaped bacteria. Because of their special growth requirements, they do not grow on usual blood agar media, but flourish on the mucosal membranes of the human respiratory tract where they adhere to the epithelial cells by fimbriae (a potential vaccine component). Nasopharyngeal carriage of Haemophilus influenzae is very common, and in healthy carriers the bacteria are usually unencapsulated. The outer membrane of Haemophilus influenzae contains lipopolysaccharide (of so called R form, without O antigen) and major outer membrane proteins. The lipopolysaccharide is a virulence determinant. An extracellular enzyme, IgA protease, is another potential virulence determinant. The outer membrane of Haemophilus influenzae is a rather ineffective barrier towards antibiotics, and thus the major determinants of antibacterial resistance in Haemophilus influenzae are plasmid-coded enzymes that inactivate the antibiotic, and changes in the target molecules.
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PMID:Unencapsulated Haemophilus influenzae--what kind of pathogen? 290 69

Serum samples from 26 normal volunteers were evaluated by isotype-specific ELISA for the presence of IgG and IgM antibodies directed at IgA. Although there were wide variations in antibody levels, anti-IgA antibodies of both isotypes were found in all individuals tested. The anti-IgA activity was detected against a variety of polymeric and monomeric IgA1 and IgA2 myeloma proteins containing both kappa and lambda light chains. By using Fab and Fc fragments generated by incubation of an IgA1 myeloma protein with IgA1 protease, it was shown that the anti-IgA activity was specific for the Fab portion of the IgA molecule. It was also demonstrated that the serum of two individuals contained both IgG and IgM activity directed at autologous affinity-purified IgA. IgM antibody levels against both whole IgA and Fab of IgA were significantly higher than IgG antibody levels. Cells producing anti-IgA antibodies of both isotypes were detected in lipopolysaccharide-stimulated human spleen.
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PMID:Normal human sera contain antibodies directed at Fab of IgA. 349 62

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-alpha and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.
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PMID:Immunoglobulin A1 protease, an exoenzyme of pathogenic Neisseriae, is a potent inducer of proinflammatory cytokines. 1052 3

Nontypeable Haemophilus influenzae is a major cause of localized respiratory tract disease and initiates infection by colonizing the nasopharynx. Colonization requires adherence to host epithelial cells, which is mediated by surface proteins such as the Hap adhesin. In this study, we identified a relationship between Hap levels in the outer membrane and lipopolysaccharide (LPS) biosynthesis enzymes. We found that mutation of the rfaF, pgmB, lgtC, kfiC, orfE, rfbP, lsgB, or lsgD genes, which are involved in the synthesis of the LPS oligosaccharide core in H. influenzae strain Rd/HapS243A, resulted in loss of Hap in the bacterial outer membrane and a decrease in hap transcript levels. In contrast, the same mutations had no effect on outer membrane localization of H. influenzae P5 or IgA1 protease or levels of p5 or iga1 transcripts, suggesting a Hap-specific effect. Elimination of the HtrA periplasmic protease resulted in a return of Hap to the outer membrane and restoration of hap transcript levels. Consistently, in lgtC phase-off bacteria, Hap was absent from the outer membrane, and hap transcript levels were reduced. Hap localization and hap transcript levels were not related to LPS size but to the functions of the LPS biosynthesis enzymes themselves. We speculate that the lack of certain LPS biosynthesis enzymes causes Hap to mislocalize and accumulate in the periplasm, where it is degraded by HtrA. This degradation then leads to a decrease in hap transcript levels. Together, these data highlight a novel interplay between Hap and LPS biosynthesis that can influence H. influenzae interactions with the host.
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PMID:Inactivation of Haemophilus influenzae lipopolysaccharide biosynthesis genes interferes with outer membrane localization of the hap autotransporter. 2228 23

Neisseria meningitidis are Gram-negative cocci, whose reservoir is exclusively human. This bacterium has several virulence factors including capsule with antiphagocytic properties, lipopolysaccharide, iron uptake system, pili and an IgA1 protease. The strains can be typed by immunological or genotypic methods. Phenotypic determination defines the serogroup, serotype, subtype and immunotype. Molecular typing, a very discriminating method, allows the determination of clonal complexes. These two epidemiological approaches allow the characterization of N. meningitidis strains. Conversely to the other strains, invasive strains belong to a very limited number of clonal complexes (CC). The evolution of the genome of N. meningitidis is the consequence of horizontal transfer of DNA occurring by transformation or recombination and leading to capsular exchanges. The distribution of the different serogroups varies according to the different countries. In France, in 2010, the serogroups B, C, W135 and Y accounted respectively for 72%, 17%, 5% and 2% of cases of invasive infections. The recent emergence of serogroup X in Niger highlights the need for continuing epidemiological surveillance.
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PMID:[Neisseria meningitidis: characterisation and epidemiology]. 2288 67