Neisseria meningitidis Serogroup X in Sub-Saharan Africa.

The epidemiology of meningococcal disease varies by geography and time. Whole-genome sequencing of Neisseria meningitidis serogroup X isolates from sub-Saharan Africa and Europe showed that serogroup X emergence in sub-Saharan Africa resulted from expansion of particular variants within clonal complex 181. Virulence of these isolates in experimental mouse models was high.

Hyperinvasive Meningococci Induce Intra-nuclear Cleavage of the NF-κB Protein p65/RelA by Meningococcal IgA Protease.

Differential modulation of NF-κB during meningococcal infection is critical in innate immune response to meningococcal disease. Non-invasive isolates of Neisseria meningitidis provoke a sustained NF-κB activation in epithelial cells. However, the hyperinvasive isolates of the ST-11 clonal complex (ST-11) only induce an early NF-κB activation followed by a sustained activation of JNK and apoptosis.

Pyrophosphate-mediated iron acquisition from transferrin in Neisseria meningitidis does not require TonB activity.

The ability to acquire iron from various sources has been demonstrated to be a major determinant in the pathogenesis of Neisseria meningitidis. Outside the cells, iron is bound to transferrin in serum, or to lactoferrin in mucosal secretions. Meningococci can extract iron from iron-loaded human transferrin by the TbpA/TbpB outer membrane complex.

Lipocalin 2 in cerebrospinal fluid as a marker of acute bacterial meningitis.

Background: Early differential diagnosis between acute bacterial and viral meningitis is problematic. We aimed to investigate whether the detection of lipocalin 2, a protein of the acute innate immunity response, may be used as a marker for acute bacterial meningitis.

Methods: Transgenic mice expressing the human transferrin were infected by intraperitoneal route and were imaged.

Molecular typing of Neisseria perflava clinical isolates.

Multilocus sequence typing and pulsed-field gel electrophoresis were used to type 22 commensal isolates of Neisseria perflava collected by swabbing from neutropenic patients. High genetic diversity was found among our N. perflava clinical isolates.

Functional impacts of the diversity of the meningococcal factor H binding protein.

Neisseria meningitidis is a human pathogenic bacterium responsible for life threatening and rapidly evolving invasive infections. Several bacterial virulence factors may play primordial roles during host-bacteria interactions. The meningococcal factor H binding protein, fHbp, interacts with the complement negative regulator, factor H (fH), to enhance meningococcal survival.

Late repression of NF-κB activity by invasive but not non-invasive meningococcal isolates is required to display apoptosis of epithelial cells.

Meningococcal invasive isolates of the ST-11 clonal complex are most frequently associated with disease and rarely found in carriers. Unlike carriage isolates, invasive isolates induce apoptosis in epithelial cells through the TNF-α signaling pathway. While invasive and non-invasive isolates are both able to trigger the TLR4/MyD88 pathway in lipooligosaccharide (LOS)-dependant manner, we show that only non-invasive isolates were able to induce sustained NF-κB activity in infected epithelial cells.

Experimental meningococcal sepsis in congenic transgenic mice expressing human transferrin.

Severe meningococcal sepsis is still of high morbidity and mortality. Its management may be improved by an experimental model allowing better understanding of its pathophysiology. We developed an animal model of meningococcal sepsis in transgenic BALB/c mice expressing human transferrin.

Emergence of new virulent Neisseria meningitidis serogroup C sequence type 11 isolates in France.

In France, there have been variations in the incidence of invasive meningococcal infection due to serogroup C isolates. Infection peaks were observed in 1992 and 2003 that involved isolates of phenotypes C:2a:P1.5,2 and/or C:2a:P1.

Influenza A virus neuraminidase enhances meningococcal adhesion to epithelial cells through interaction with sialic acid-containing meningococcal capsules.

The underlying mechanisms of the epidemiological association between influenza virus infections and Neisseria meningitidis invasive infections are not fully understood. Here we report that adhesion of N. meningitidis to human Hec-1-B epithelial cells is enhanced by influenza A virus (IAV) infection.

Differential modulation of TNF-alpha-induced apoptosis by Neisseria meningitidis.

Infections by Neisseria meningitidis show duality between frequent asymptomatic carriage and occasional life-threatening disease. Bacterial and host factors involved in this balance are not fully understood. Cytopathic effects and cell damage may prelude to pathogenesis of isolates belonging to hyper-invasive lineages.

Transgenic mice expressing human transferrin as a model for meningococcal infection.

The pathogenesis of meningococcal disease is poorly understood due to the lack of a relevant animal model. Moreover, the use of animal models is not optimal as most meningococcal virulence determinants recognize receptors that are specifically expressed in human tissues. One major element of the host specificity is the system of meningococcal iron uptake by transferrin-binding proteins that bind specifically human transferrin but not murine transferrin.

Meningococcal meningitis: unprecedented incidence of serogroup X-related cases in 2006 in Niger.

Background: In Niger, epidemic meningococcal meningitis is primarily caused by Neisseria meningitidis (Nm) serogroup A. However, since 2002, Nm serogroup W135 has been considered to be a major threat that has not yet been realized, and an unprecedented incidence of Nm serogroup X (NmX) meningitis was observed in 2006.

Methods: Meningitis surveillance in Niger is performed on the basis of reporting of clinically suspected cases.

Continuing diversification of Neisseria meningitidis W135 as a primary cause of meningococcal disease after emergence of the serogroup in 2000.

The occurrence of a clonal outbreak of serogroup W135 (of the electrophoretic type 37 [ET-37] clonal complex) meningococcal disease among Hajj pilgrims in 2000 has led to enhanced surveillance of the evolution of this particular serogroup, formerly considered rare, in invasive infections. Since the first case of meningococcal disease due to a serogroup W135 strain was detected in France in 1994, all isolates were characterized phenotypically. We further used phenotypic and genotypic approaches to type the 101 serogroup W135 strains isolated from patients with invasive meningococcal diseases in France in 2001 and 2002.

Analysis in vitro and in vivo of the transcriptional regulator CrgA of Neisseria meningitidis upon contact with target cells.

Contact between CrgA, a LysR-like regulatory protein in Neisseria meningitidis, and DNA is involved in the repression of several bacterial genes upon contact with epithelial cells. We used a defined in vitro system containing crgA promoter, purified RNA polymerase (RNAP) and purified CrgA protein to demonstrate that CrgA was directly responsible for this transcriptional repression. Interaction between the C-terminal domain of CrgA and the RNAP led to the production of short abortive transcripts, suggesting that CrgA may act by preventing RNAP from clearing the promoter.

The role of particular strains of Neisseria meningitidis in meningococcal arthritis, pericarditis, and pneumonia.

The clinical presentations of meningococcal diseases other than meningitis or meningococcemia may lead to erroneous diagnosis. Although several reports have described unusual meningococcal diseases, the Neisseria meningitidis strains involved in these forms have been poorly characterized. In this study, meningococcal arthritis and pericarditis were confirmed by isolation of N.

Differential expression of genes that harbor a common regulatory element in Neisseria meningitidis upon contact with target cells.

The expression of several genes in Neisseria meningitidis upon contact with epithelial cells was associated with the presence of the contact regulatory elements of NEISSERIA: These genes are involved in various aspects of meningococcal biology and could be coordinately regulated upon contact with target cells.

Down-regulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein.

The initial attachment of Neisseria meningitidis to the target cell surface appears to be largely pilus depend-ent in capsulated bacteria. Intimate adhesion subsequently occurs to permit colonization. We recently reported that insertional inactivation of the crgA gene, which encodes a transcriptional regulator belonging to the LysR family, decreased meningococcal adhesion to epithelial cells and abolished intimate adhesion.