ArticleJournal of biomedical science2022
HrpA anchors meningococci to the dynein motor and affects the balance between apoptosis and pyroptosis.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Effects of surface-exposed sialic acid and LOS outer core on the ability of native Neisseria meningitidis outer membrane vesicles (nOMVs) to induce cytokine expression and pyroptotic pathways in THP-1-derived macrophages.Scientific reports · 2025Article
- Generation and characterization of a DYNLT1-knockout mouse model reveals electrophysiological alterations and potential mechanistic contributors to atrial fibrillation.Biology open · 2025Article
- Lysosomal Dysfunction in Amyotrophic Lateral Sclerosis: A Familial Case Linked to the p.G376DInternational journal of molecular sciences · 2025Article
- Review
- Combined transcriptome and metabolome analysis reveals the regulatory network of histidine kinase QseC in the two-component system ofFrontiers in microbiology · 2025Article
- Targeting PANoptosis in Bacterial-Induced Inflammatory Diseases: Mechanisms and Therapeutic Interventions.Journal of inflammation research · 2025Review
- Review
- Review
- Mitochondrial Quality Control Processes at the Crossroads of Cell Death and Survival: Mechanisms and Signaling Pathways.International journal of molecular sciences · 2024Review
- Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?International journal of molecular sciences · 2024Review
- Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells.Cell communication and signaling : CCS · 2024Article
- Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundIn Neisseria meningitidis the HrpA/HrpB two-partner secretion system (TPS) was implicated in diverse functions including meningococcal competition, biofilm formation, adherence to epithelial cells, intracellular survival and vacuolar escape. These diverse functions could be attributed to distinct domains of secreted HrpA.
methodsA yeast two-hybrid screening, in vitro pull-down assay and immunofluorescence microscopy experiments were used to investigate the interaction between HrpA and the dynein light-chain, Tctex-type 1 (DYNLT1). In silico modeling was used to analyze HrpA structure. Western blot analysis was used to investigate apoptotic and pyroptotic markers.
resultsThe HrpA carboxy-terminal region acts as a manganese-dependent cell lysin, while the results of a yeast two-hybrid screening demonstrated that the HrpA middle region has the ability to bind the dynein light-chain, Tctex-type 1 (DYNLT1). This interaction was confirmed by in vitro pull-down assay and immunofluorescence microscopy experiments showing co-localization of N. meningitidis with DYNLT1 in infected epithelial cells. In silico modeling revealed that the HrpA-M interface interacting with the DYNLT1 has similarity with capsid proteins of neurotropic viruses that interact with the DYNLT1. Indeed, we found that HrpA plays a key role in infection of and meningococcal trafficking within neuronal cells, and is implicated in the modulation of the balance between apoptosis and pyroptosis.
conclusionsOur findings revealed that N. meningitidis is able to effectively infect and survive in neuronal cells, and that this ability is dependent on HrpA, which establishes a direct protein-protein interaction with DYNLTI in these cells, suggesting that the HrpA interaction with dynein could be fundamental for N. meningitidis spreading inside the neurons. Moreover, we found that the balance between apoptotic and pyroptotic pathways is heavily affected by HrpA.
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