Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Signaling of Neisseria meningitidis MC58 mutants to primary human umbilical vein endothelial cells (HUVEC)

ABSTRACT: We examined the adherence-mediated signaling of meningococci to human cells by comparing gene expression profiles of primary human umbilical vein endothelial cells (HUVEC) infected by piliated and adherent wild-type (WT), frpC/frpA-deficient mutant, or the non-adherent (ΔpilD) N. meningitidis MC58 bacteria defective in production of the type IV pilus, respectively. Surprisingly, no significant difference was found between the transcriptomes of HUVECs infected by bacteria producing, or not the RTX FrpC and FrpA proteins, thus failing to provide any hints on their biological activity. In contrast, pili-mediated adhesion of meningococci resulted in alterations of expression levels of human genes known to regulate apoptosis, cell proliferation, inflammatory response or adhesion. In particular, genes for signaling pathway proteins involved in early embryonic development, such as transforming growth factor-β (TGF-β)/Smad, Wnt/β-catenin, and Notch/Jagged were found to be upregulated upon adhesion of N. meningitidis together with genes for a number of transcription factors. This reveals that adhering piliated meningocci manipulate signaling pathways controlling human cell proliferation, survival and defense mechanisms, while establishing a commensal relationship with the host. Keywords: time course, infection response, genetic modification

ORGANISM(S): Homo sapiens

PROVIDER: GSE4646 | GEO | 2006/09/01

SECONDARY ACCESSION(S): PRJNA95283

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-actinin-4

Project description:Neisseria meningitidis (meningococcus) is an invasive bacterial pathogen that colonizes human vessels, causing thrombotic lesions and meningitis. Establishment of tight interactions with endothelial cells is crucial for meningococci to resist hemodynamic forces. Two endothelial receptors, CD147 and the β2-adrenergic receptor (β2AR), are sequentially engaged by meningococci to adhere and promote signaling events leading to vascular colonization, but their spatiotemporal coordination is unknown. Here we report that CD147 and β2AR form constitutive hetero-oligomeric complexes. The scaffolding protein alpha-actinin-4 directly binds to the cytosolic tail of CD147 and governs the assembly of CD147/β2AR complexes in highly-ordered clusters at bacterial adhesion sites. This multi-molecular assembly process increases the binding strength of meningococci to endothelial cells under shear stress, and creates molecular platforms for the elongation of membrane protrusions surrounding adherent bacteria. Thus, the specific organization of cellular receptors has major impacts on host-pathogen interaction.

2017-07-10 | PXD006212 | Pride

Transcription profiling of human HUVEC cell line infected with Neisseria meningitidis wild type and mutants vs uninfected sampled at 3 time points reveals meningococcal adhesion suppresses proapoptotic gene expression and promotes expression of genes supporting early embryonic and cytoprotective signaling of human endothelial cells.

Project description:Time courses of gene expression profiles of primary human umbilical vein endothelial cells (HUVEC) during infection with piliated and adherent wild-type (WT), frpC/frpA-deficient mutant, or the non-adherent (?pilD) Neisseria meningitidis MC58 bacteria defective in production of the type IV pilus, were analyzed respectively. Total RNA isolated from uninfected HUVEC (reference) and HUVEC after 1, 4 or 6 hours of infection with N. meningitidis mutants was labeled according to standard Affymetrix protocol and hybridized to HG-U133A GeneChips. Data were analyzed by Robust Multi-array Analysis algorithm. For every condition at least two biological replicates were analyzed, totally representing 23 Affymetrix GeneChips.

2007-10-26 | E-GEOD-4646 | biostudies-arrayexpress

Transcriptional profiling of Neisseria meningitidis Interacting with Human Epithelial Cells in a Long-Term In Vitro Colonization Model

Project description:Neisseria meningitidis is a commensal of humans that can colonize the nasopharyngeal epithelium for weeks to months and occasionally invades to cause life-threatening septicemia and meningitis. Comparatively little is known about meningococcal gene expression during colonization beyond those first few hours. In this study, the transcriptome of adherent serogroup B N. meningitidis strain MC58 was determined at intervals during prolonged cocultivation with confluent monolayers of the human respiratory epithelial cell line 16HBE14. At different time points up to 21 days, 7 to 14% of the meningococcal genome was found to be differentially regulated. The transcriptome of adherent meningococci obtained after 4 h of coculture was markedly different from that obtained after prolonged cocultivation (24 h, 96 h, and 21 days). Genes persistently upregulated during prolonged cocultivation included three genes (hfq, misR/phoP, and lrp) encoding global regulatory proteins. Many genes encoding known adhesins involved in epithelial adherence were upregulated, including those of a novel locus (spanning NMB0342 to NMB0348 [NMB0342-NMB0348]) encoding epithelial cell-adhesive function. Sixteen genes (including porA, porB, rmpM, and fbpA) encoding proteins previously identified by their immunoreactivity to sera from individuals colonized long term with serogroup B meningococci were also upregulated during prolonged cocultivation, indicating that our system models growth conditions in vivo during the commensal state. Surface-expressed proteins downregulated in the nasopharynx (and thus less subject to selection pressure) but upregulated in the bloodstream (and thus vulnerable to antibody-mediated bactericidal activity) should be interesting candidate vaccine antigens, and in this study, three new proteins fulfilling these criteria have been identified: NMB0497, NMB0866, and NMB1882. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-141]

2013-11-02 | E-BUGS-141 | biostudies-arrayexpress

Determination of the FarR regulon

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.

2011-02-11 | GSE20643 | GEO

Transcriptional profiling of NMB0419 mutant of Neisseria meningitidis MC58

Project description:Neisseria meningitidis is an obligate commensal colonising the human nasopharynx and occasionally invades the bloodstream causing life-threatening meningitis and septicaemia. The gene NMB0419 on the genome of N. meningitidis MC58 encodes a putative Sel1-like repeat (SLR) containing protein, which has been implicated in mediating meningococcal invasion of epithelial cells. We prepared RNA samples from N. meningitidis MC58 (WT) and its isogenic mutant of NMB0419 grown to log phase in in-vitro culture. The RNA samples were subjected to RNA sequencing. The resulting transcriptomes were compared to determine the genes that differentially expressed in NMB0419 mutant.

2017-03-07 | GSE81572 | GEO

CGH result of Neisseria meningitidis ST-7 isolates

Project description:Neisseria meningitidis is a major cause of bacterial meningitis and septicemia worldwide. Seven new serogroup C meningococci were isolated from two provinces of China in January, 2006. Their PorA VR types were P1.20, 9. Multilocus sequence typing results indicated that they all belonged to ST-7. It is a new serogroup C N. meningitidis sequence type clone identified in China. Here we also present the results of a genomic comparison of these isolates with other 15 N. meningitidis serogroup A and B isolates, which belonged to ST-7, based on comparative genomic hybridization analysis. The data described here would be helpful to monitor the spread of this new serogroup C meningococci sequence type clone in China and worldwide. Keywords: comparative genomic hybridization

2007-10-11 | GSE7331 | GEO

Transcription profiling by array of Transcriptional profiling of serogroup B Neisseria meningitidis growing in human blood: an approach to vaccine antigen discovery.

Project description:Neisseria meningitidis is a nasopharyngeal commensal of humans which occasionally invades the blood to cause septicaemia. The transcriptome of N. meningitidis strain MC58 grown in human blood for up to 4 hours was determined and around 10% of the genome was found to be differentially regulated. The nuo, pet and atp operons, involved in energy metabolism, were up-regulated, while many house-keeping genes were down-regulated. Genes encoding protein chaperones and proteases, involved in the stress response; complement resistant genes encoding enzymes for LOS sialylation and biosynthesis; and fHbp (NMB1870) and nspA (NMB0663), encoding vaccine candidates, were all up-regulated. Genes for glutamate uptake and metabolism, and biosynthesis of purine and pyrimidine were also up-regulated. Blood grown meningococci are under stress and undergo a metabolic adaptation and energy conservation strategy. The localisation of four putative outer membrane proteins encoded by genes found to be up-regulated in blood was assessed by FACS using polyclonal mouse antisera, and one (NMB0390) showed evidence of surface expression, supporting its vaccine candidacy. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-121]

2012-11-06 | E-BUGS-121 | biostudies-arrayexpress

Zur regulon of Neisseria meningitidis

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)

2012-10-05 | GSE38033 | GEO

Proteomic profiling of human monocytes stimulated in vitro with N. meningitidis

Project description:Meningococcal sepsis is an overwhelming form of the sepsis syndrome which may cause mortality within 12-24 hours in previously healthy children and adults, where the causative infectious agent is N. meningitidis, an obligate human pathogen. The genomic changes induced by N. meningitidis are modulated by the anti-inflammatory cytokine interleukin-10 (IL-10), which is present in large quantities in plasma from patients with meningococcal sepsis. This present study investigated kinase activities in human monocytes stimulated by N. meningitidis and IL-10. The first aim was to identify array peptides that could indicate which signaling pathways were activated or inhibited by the host response to the meningococci. The second aim was to detect whether IL-10 affected N. meningitidis-nduced phosphorylation of array peptides, in order to identify potential targets of the IL-10 anti-inflammatory response. We approached this using a strategy where elutriation-purified human monocytes are stimulated in vitro with N. meningitidis and IL-10, with concentrations corresponding to previously measured levels in patients with fulminant meningococcal septicemia. This work examined activation or inhibition of signaling pathways mediated by tyrosine kinases when purified human monocytes are in vitro incubated with N. meningitidis in the presence or absence of IL-10.

2017-12-15 | E-MTAB-4795 | biostudies-arrayexpress

Transcriptome analysis of Neisseria meningitidis strain MC58 in human whole blood

Project description:Transcriptome analysis of Neisseria meningitidis strain MC58 during a time course growth in human whole blood

2011-06-09 | E-TABM-1115 | biostudies-arrayexpress