ArticleCellular microbiology2015
Nuclear trafficking, histone cleavage and induction of apoptosis by the meningococcal App and MspA autotransporters.
Article in Cellular microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Hijacked epigenomes: how bacterial effectors rewrite host gene expression.Archives of microbiology · 2026Review
- Identification of candidate nucleomodulins in ESKAPE bacteria -Frontiers in cellular and infection microbiology · 2026Article
- Review
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Phylogenetic Classification and Functional Review of Autotransporters.Frontiers in immunology · 2022Review
- The Host-Pathogen Interactions and Epicellular Lifestyle ofFrontiers in cellular and infection microbiology · 2022Review
- Modelling evolutionary pathways for commensalism and hypervirulence inMicrobial genomics · 2021Article
- Bacterial nucleomodulins: A coevolutionary adaptation to the eukaryotic command center.PLoS pathogens · 2021Review
- Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry byInternational journal of molecular sciences · 2020Review
- Review
- Article
- Biological Functions of the Secretome ofFrontiers in cellular and infection microbiology · 2017Review
- Hyperinvasive Meningococci Induce Intra-nuclear Cleavage of the NF-κB Protein p65/RelA by Meningococcal IgA Protease.PLoS pathogens · 2015Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neisseria meningitidis, a major cause of bacterial meningitis and septicaemia, secretes multiple virulence factors, including the adhesion and penetration protein (App) and meningococcal serine protease A (MspA). Both are conserved, immunogenic, type Va autotransporters harbouring S6-family serine endopeptidase domains. Previous work suggested that both could mediate adherence to human cells, but their precise contribution to meningococcal pathogenesis was unclear. Here, we confirm that App and MspA are in vivo virulence factors since human CD46-expressing transgenic mice infected with meningococcal mutants lacking App, MspA or both had improved survival rates compared with mice infected with wild type. Confocal imaging showed that App and MspA were internalized by human cells and trafficked to the nucleus. Cross-linking and enzyme-linked immuno assay (ELISA) confirmed that mannose receptor (MR), transferrin receptor 1 (TfR1) and histones interact with MspA and App. Dendritic cell (DC) uptake could be blocked using mannan and transferrin, the specific physiological ligands for MR and TfR1, whereas in vitro clipping assays confirmed the ability of both proteins to proteolytically cleave the core histone H3. Finally, we show that App and MspA induce a dose-dependent increase in DC death via caspase-dependent apoptosis. Our data provide novel insights into the roles of App and MspA in meningococcal infection.
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