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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenic species Neisseria meningitidis and Neisseria gonorrhoeae cause dramatically different diseases despite strong relatedness at the genetic and biochemical levels. N. meningitidis can cross the blood-brain barrier to cause meningitis and has a propensity for toxic septicemia unlike N. gonorrhoeae. We previously used subtractive hybridization to identify DNA sequences which might encode functions specific to bacteremia and invasion of the meninges because they are specific to N. meningitidis and absent from N. gonorrhoeae. In this report we show that these sequences mark eight genetic islands that range in size from 1.8 to 40 kb and whose chromosomal location is constant. Five of these genetic islands were conserved within a representative set of strains and/or carried genes with homologies to known virulence factors in other species. These were deleted, and the mutants were tested for correlates of virulence in vitro and in vivo. This strategy identified one island, region 8, which is needed to induce bacteremia in an infant rat model of meningococcal infection. Region 8 encodes a putative siderophore receptor and a disulfide oxidoreductase. None of the deleted mutants was modified in its resistance to the bactericidal effect of serum. Neither were the mutant strains altered in their ability to interact with endothelial cells, suggesting that such interactions are not encoded by large genetic islands in N. meningitidis.
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PMID:Molecular and biological analysis of eight genetic islands that distinguish Neisseria meningitidis from the closely related pathogen Neisseria gonorrhoeae. 1072 5

The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essential step in pathogenesis, we analyzed a library of 2,850 insertional mutants of N. meningitidis for their capacity to cause systemic infection in an infant rat model. The library was constructed by in vitro modification of Neisseria genomic DNA with the purified components of Tn10 transposition. We identified 73 genes in the N. meningitidis genome that are essential for bacteremic disease. Eight insertions were in genes encoding known pathogenicity factors. Involvement of the remaining 65 genes in meningocoocal pathogenesis has not been demonstrated previously, and the identification of these genes provides insights into the pathogenic mechanisms that underlie meningococcal infection. Our results provide a genome-wide analysis of the attributes of N. meningitidis required for disseminated infection, and may lead to new interventions to prevent and treat meningococcal infection.
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PMID:Functional genomics of Neisseria meningitidis pathogenesis. 1106 28

Mortality of meningococcal septicemia remains high in spite of the improvement of antibiotics treatment and critical care medicine. A 23-year-old male, who had been well until a day earlier, was admitted to the hospital because of a high-grade fever and headache. On the second hospital day, he was still febrile, and it was confirmed that he had disseminated intravascular coagulation. There was no purpuric skin lesion, and a lumbar puncture revealed no abnormality. The condition was complicated by a splenic infarction on the second hospital day, and he suffered a pulmonary infarction on the 8th hospital day. The blood culture was positive for Neisseria meningitidis, making the diagnosis meningococcal septicemia. He was successfully treated with antibiotics and intensive care. Although meningococcocemia in adults is relatively rare in Japan, the disease mortality is still high even in the modern era. Then, once the diagnosis is suspected, it is essential to keep in mind that meningococcal infection requires early recognition of the disease process, prompt initiation of adequate antiinfectious therapy and intensive treatment of multiorgan failure.
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PMID:[Meningococcocemia complicated by disseminated intravascular coagulation, splenic infarction and pulmonary thromboembolism in a young adult: case report]. 1135 26

Neisseria meningitidis is known to cause a spectrum of diseases, including bacteraemia without sepsis, meningococcaemia without meningitis, meningitis with or without meningococcaemia, and chronic meningococcaemia. Less common manifestations of meningococcal infection include pharyngitis, pneumonia, pericarditis, urethritis and arthritis. To our knowledge, there have been no previous reports of N. meningitidis causing prosthetic joint infection. Herein, we report a case of primary meningococcal arthritis in a woman with a prosthetic knee joint. After surgical drainage the prosthesis was retained and the patient received appropriate and prolonged antibiotic treatment. The outcome was favourable, as with primary meningococcal arthritis affecting native joints.
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PMID:Primary meningococcal arthritis in a prosthetic knee joint. 1154 73

Explosion of knowledge both in human genomics and in host inflammatory response explains the increasing interest in infectious disease genetics over the last 5 years. However, twin and adoptee studies have suggested more than 15 years ago, that host genetic factors are major determinants of susceptibility to infectious diseases in humans. Recently, candidate gene studies (association studies) and human genomewide analysis have been used to identify infectious diseases susceptibility and resistance genes. Rarely, a single gene defect has been directly related to devastating consequences such as interferon-gamma receptor mutations leading to fatal infections with ubiquitous mycobacteria. For clinical practice, gene polymorphisms of specific host immune defence elements appear to be of major importance. These genetic variants, which modify the regulation or function of the mediators, have been associated with susceptibility and/or outcome of severe sepsis and septic shock. All steps of the host response to bacteria may be affected by genetic factors. For example, Fc gamma receptor, Toll like receptor or mannose binding protein mutations have been shown to modify the detection of pathogens leading to pneumococcal severe infections, Gram-negative bacteria septic shock, and meningococcal disease, respectively. Polymorphisms of cytokine genes (TNF-alpha, TNF-beta, IL-1-ra) have been reported to influence the level of secreted mediators and to unbalance the inflammatory cascade. Coagulation response to sepsis may also be affected by gene variants such as the plaminogen activator inhibitor 1 (PAI-1) common functional polymorphism which increases the risk of death from meningococcal infection or severe trauma. The impact of these findings on the understanding of infectious disease pathogenesis and on the design of future preventive and therapeutic strategies should be considerable.
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PMID:[Role of host response during severe bacterial infection]. 1158 14

Lipopolysaccharides in the outer membrane of Neisseria meningitidis are key molecules that induce inflammation and cause meningitis and shock. Mutant strains, with altered lipid A, the toxic moiety of lipopolysaccharide, or completely lacking lipopolysaccharide, induce significantly less inflammation than wild-type strains. Polymorphism of the Fc gamma receptors and interleukin-10 gene but not of the Toll-like receptor 4 may influence the development of meningococcal infection. Mannan-binding lectin is involved in complement activation, the regulation of adhesion molecules and cytokine production induced by meningococci. The activation of protein C by the thrombomodulin protein C receptor complex on the endothelial cell surface appears to be reduced in meningococcal sepsis but is still sufficient to convert protein C to activated protein C in patients treated with concentrated protein C.
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PMID:Current concepts in the role of the host response in Neisseria meningitidis septic shock. 1201 58

Infections with Neisseria meningitidis are characterized by life-threatening meningitis and septicemia. The meningococcal porin proteins from serogroup B meningococci have been identified as candidates for inclusion in vaccines to prevent such infections. In this study, we investigated the vaccine potential of the PorB porin protein free of other meningococcal components. The porB gene from a strain of Neisseria meningitidis expressing the class 3 outer membrane porin protein (PorB3) was cloned into the pRSETB vector, and the protein was expressed at high levels in a heterologous host Escherichia coli. The recombinant protein was purified to homogeneity by affinity chromatography and used for immunization after incorporation into liposomes and into micelles composed either of zwitterionic detergent or nondetergent sulfobetaine. The immunogenicity of these preparations was compared to recombinant PorB protein adsorbed to Al(OH)(3) adjuvant as a control. Although sera raised against the protein adsorbed to Al(OH)(3) reacted with the purified recombinant protein, sera raised against liposomes and micelles showed greater activity with native protein, as measured by enzyme immunoassay with outer membranes and by whole-cell immunofluorescence. Reactivity with native protein was considerably enhanced by incorporation of the adjuvant monophosphoryl lipid A into the liposome or micelle preparations. Recognition of the native protein was in a serotype-specific manner and was associated with the ability of the antisera to promote high levels of serotype-specific complement-mediated killing of meningococci. These results demonstrate that the PorB protein should be considered as a component of a vaccine designed to prevent serogroup B meningococcal infection.
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PMID:Immunization with the recombinant PorB outer membrane protein induces a bactericidal immune response against Neisseria meningitidis. 1211 8

Neisseria meningitidis is the cause of septicemia and meningococcal meningitis. During the course of infection, N. meningitidis encounters multiple environments within its host, which makes rapid adaptation to environmental changes a crucial factor for neisserial pathogenicity. Employing oligonucleotide-based DNA microarrays, we analyzed the transcriptome of N. meningitidis during two key steps of meningococcal infection, i.e., the interaction with epithelial cells (HeLa cells) and endothelial cells (human brain microvascular endothelial cells). Seventy-two genes were differentially regulated after contact with epithelial cells, and 48 genes were differentially regulated after contact with endothelial cells, including a considerable proportion of well-known virulence genes. While a considerable number of genes were in concordance between bacteria adherent to both cell types, we identified several open reading frames that were differentially regulated in only one system. The data obtained with this novel approach may provide insight into the pathogenicity mechanisms of N. meningitidis and could demonstrate the importance of gene regulation on the transcriptional level during different stages of meningococcal infection.
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PMID:Transcriptome analysis of Neisseria meningitidis during infection. 1248 52

The clinical spectrum of meningococcal infection ranges from asymptomatic carriage to fulminant sepsis, with meningitis and septicemia being well-recognized clinical presentations. Meningococcal arthritis as a complication of Neisseria meningitidis infection occurs in about 2-10% of cases, whereas primary meningococcal arthritis (PMA) is a relatively rare phenomenon, even in children. We report here a case of meningococcal infection in an immunocompetent adolescent suffering from acute pain of the right hip as the only symptom upon presentation at the hospital. In such a situation, meningococci are not usually considered as a possible causative agent.
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PMID:Primary meningococcal arthritis of the hip in an immunocompetent adolescent. 1272 54

As the central component of the human endotoxin sensor, Toll-like receptor 4 (TLR4) functions in the early detection and response to Gram-negative infection. We therefore examined a large collection of patients with meningococcal sepsis, comparing the frequency of rare TLR4 coding changes to those in an ethnically matched control population. TLR2 sequences were also acquired and compared. Total nucleotide variation at TLR4 and TLR2 loci was assayed by using a novel computational method. A total of 3.01 megabases of coding sequence was captured at these loci from white subjects with or without meningococcal disease. Authentic mutations were found and high-quality, bidirectional coverage was measured across the coding region by using mutationseeker, a program specifically designed to assay locus-specific genetic load. Using a method that obviates the confounding effect of linkage disequilibrium, we observed that rare heterozygous missense mutations of TLR4 contribute to the development of systemic meningococcal disease among white populations of the southern United Kingdom (P = 0.02; odds ratio 8.2). When results from all white populations were pooled, an overwhelmingly significant excess of such mutations was observed among individuals with disease (P = 2 x 10(-6); odds ratio 27.0). The common white TLR4 variant (TLR4B), synonymous TLR4 substitutions, and variant TLR2 alleles were not significantly over-represented among patients with systemic meningococcal infections. No single variant of TLR4 was significantly over-represented in the meningococcal population. Collectively, however, rare TLR4 coding variants were markedly over-represented. Sensing via TLR4 probably contributes to the early containment of meningococcal infection, and sensing defects create increased risk of disease.
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PMID:Assay of locus-specific genetic load implicates rare Toll-like receptor 4 mutations in meningococcal susceptibility. 1273 Mar 65


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