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Characterization of ST-4821 complex, a unique Neisseria meningitidis clone

ABSTRACT: Neisseria meningitidis is the leading cause of bacterial meningitis and septicemia worldwide. The novel ST-4821 clonal complex caused several serogroup C meningococcal outbreaks unexpectedly during 2003–2005 in China. We fabricated a whole-genome microarray of Chinese N. meningitidis serogroup C representative isolate 053442 and characterized 27 ST-4821 complex isolates which were isolated from different serogroups using comparative genomic hybridization (CGH) analysis. This paper provides important clues which are helpful to understand the genome composition and genetic background of different serogroups isolates, and possess significant meaning to the study of the newly emerged hyperinvasive lineage. Keywords: comparative genomic hybridization

ORGANISM(S): Neisseria meningitidis

PROVIDER: GSE7780 | GEO | 2007/11/28

SECONDARY ACCESSION(S): PRJNA99801

REPOSITORIES: GEO

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Characterization of ST-4821 complex, a unique Neisseria meningitidis clone

Project description:Neisseria meningitidis is the leading cause of bacterial meningitis and septicemia worldwide. The novel ST-4821 clonal complex caused several serogroup C meningococcal outbreaks unexpectedly during 2003â2005 in China. We fabricated a whole-genome microarray of Chinese N. meningitidis serogroup C representative isolate 053442 and characterized 27 ST-4821 complex isolates which were isolated from different serogroups using comparative genomic hybridization (CGH) analysis. This paper provides important clues which are helpful to understand the genome composition and genetic background of different serogroups isolates, and possess significant meaning to the study of the newly emerged hyperinvasive lineage. To further understand the genome diversity of ST-4821 complex isolates, CGH analysis was employed to compare the genomic content of 053442 with those of 27 ST-4821 complex isolates which were isolated from 14 provinces of China during 1977â2005.

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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 To compare the genome compositions of these menC ST-7 isolates with those of menC ST-4821 isolates, menA ST-7 isolates and menB ST-7 isolates, we performed comparative genomic hybridization (CGH) analysis among 17 N. meningitidis isolates (including two newly identified menC ST-7 isolates) using an updated version of the whole-genome microarray of N. meningitidis serogroup C isolate 053442 .

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Serum resistance of Neisseria meningitidis strains of the ST-41/44 clonal complex is influenced by a homopolymeric adenosine tract in the promotor region of the nspA gene

Project description:Although usually a harmless colonizer of the human nasopharynx, Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator fH. Meningococcal strains are highly diverse and are categorized by their serogroup and multilocus sequence typing. The sequence type 41/44 clonal complex makes up a major proportion of serogroup B meningococcal disease worldwide, but it is also common in asymptomatic carriers. Proteome analysis of a serum resistant isolate from invasive meningococcal disease and two less resistant isolates from healthy carriers identified NspA as the sole protein consistently expressed more abundantly in the invasive isolate. Knock-out of nspA reduced serum resistance, accompanied by stronger deposition of membrane attack complex (C5b9). High or low expression of NspA was associated with sequence variation within a homopolymeric tract located in the -10/-35 region of the nspA promotor: A tract with 5 adenosines dictated low NspA expression, whereas a 6-adenosine motif led to high NspA expression. High levels of NspA correlated with high factor H sequestration onto the bacteria. We could not link the homopolymeric tract length to phase variation, unlike described for other N. meningitidis surface proteins with similar sequence motifs. Epidemiological evidence from carriage and disease isolates indicates that NspA contributes to serum resistance, but is not a prerequisite for invasive disease. Thus, the lineage ST-41/44 meningococcal strains are heterogenous in their NspA expression.

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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.

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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]

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