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 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
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
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 .
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.
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.
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:The Gram-negative bacterium Neisseria meningitidis causes meningitis in humans and has been demonstrated to manipulate or alter host signalling pathways during infection of the central nervous system. In this study, the phosphoproteome of an in vitro model of the blood-cerebrospinal fluid barrier was investigated during infection with the Neisseria meningitidis serogroup B (NmB) strain MC58 in presence and absence of the bacterial capsule. We show that the capsule deficient mutant has a higher impact on the phosphoproteome of the infected cells and identify potentially regulated pathways and cellular processes during infection.
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: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.