Project description:The human-specific, Gram-negative bacterium Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis world-wide. It has been described that Nm can enter the central nervous system via the blood-cerebrospinal fluid barrier (BCSFB), which is constituted by the epithelial cells of the choroid plexus. Using a recently established in vitro model of the human BCSFB based on human malignant choroid plexus papilloma (HIBCPP) cells we investigated the cellular response of HIBCPP cells challenged with the meningitis-causing Nm strain MC58. In comparison we analysed the answer to the closely related unencapsulated carrier isolate Nm M-NM-114. Transcriptome analysis revealed a stronger transcriptional response after infection with strain MC58, in particular with its capsule deficient mutant MC58siaD-, which correlated with bacterial invasion levels. Expression evaluation and Gene Set Enrichment Analysis pointed to a NF-M-NM-:B-mediated pro-inflammatory immune response involving up-regulation of the transcription factor IM-NM-:BM-NM-6. Consistent with this, infected cells secreted significant levels of pro-inflammatory chemokines and cytokines, among others, IL8, CXCL1-3 and the IM-NM-:BM-NM-6 target gene product IL6. Expression profile of pattern recognition receptors in HIBCPP cells and the response to specific agonists indicates that TLR2 rather than TLR4 is involved in the cellular reaction following Nm infection. Human malignant choroid plexus papilloma (HIBCPP) cells were infected from the basolateral side with the meningitis-causing Neisseria meningitidis disease isolate MC58, its non-capsulated mutant MC58siaD- and the Neisseria meningitidis carrier isolate M-NM-114 for 4 h.The transcriptional response of HIBCPP cells to the different Neisseria meningitidis strains was evaluated by microarray analysis. Untreated HIBCPP cells served as control. Three replicates of each condition were analysed.
Project description:Microarray comparative genome hybridization (mCGH) data was collected from one Neisseria cinerea, two Neisseria lactamica, two Neisseria gonorrhoeae, and 48 Neisseria meningitidis isolates. For N. meningitidis, these isolates are from diverse clonal complexes, invasive and carriage strains, and all major serogroups. The microarray platform represented N. meningitidis strains MC58, Z2491, and FAM18 and N. gonorrhoeae FA1090.
Project description:Baart2007 - Genome-scale metabolic network of
Neisseria meningitidis (iGB555)
This model is described in the article:
Modeling Neisseria
meningitidis metabolism: from genome to metabolic fluxes.
Baart GJ, Zomer B, de Haan A, van
der Pol LA, Beuvery EC, Tramper J, Martens DE.
Genome Biol. 2007; 8(7): R136
Abstract:
BACKGROUND: Neisseria meningitidis is a human pathogen that
can infect diverse sites within the human host. The major
diseases caused by N. meningitidis are responsible for death
and disability, especially in young infants. In general, most
of the recent work on N. meningitidis focuses on potential
antigens and their functions, immunogenicity, and pathogenicity
mechanisms. Very little work has been carried out on Neisseria
primary metabolism over the past 25 years. RESULTS: Using the
genomic database of N. meningitidis serogroup B together with
biochemical and physiological information in the literature we
constructed a genome-scale flux model for the primary
metabolism of N. meningitidis. The validity of a simplified
metabolic network derived from the genome-scale metabolic
network was checked using flux-balance analysis in chemostat
cultures. Several useful predictions were obtained from in
silico experiments, including substrate preference. A minimal
medium for growth of N. meningitidis was designed and tested
successfully in batch and chemostat cultures. CONCLUSION: The
verified metabolic model describes the primary metabolism of N.
meningitidis in a chemostat in steady state. The genome-scale
model is valuable because it offers a framework to study N.
meningitidis metabolism as a whole, or certain aspects of it,
and it can also be used for the purpose of vaccine process
development (for example, the design of growth media). The flux
distribution of the main metabolic pathways (that is, the
pentose phosphate pathway and the Entner-Douderoff pathway)
indicates that the major part of pyruvate (69%) is synthesized
through the ED-cleavage, a finding that is in good agreement
with literature.
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Project description:Whole genome DNA microarray of Neisseria meningitidis serogroup B strain MC58 and the isogenic mutant strain deficient of the transcriptional regulator FarR, MC58 ∆farR.
Project description:The zur regulon in Neisseria meningitidis was elucidated in the strain MC58 using a zur knockout strain and conditions which activate Zur ( zinc supplementation in the medium)