ArticlePLoS pathogens2013
Bacterial cytolysin during meningitis disrupts the regulation of glutamate in the brain, leading to synaptic damage.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 52 citations in OpenAlex.
- Maternal Infection Induces Neuronal Structure and Behavioural Alterations in Experimental Meningitis Rat Model.Developmental neuroscience · 2026Article
- Amino acid dysregulation in cerebrospinal fluid of stroke patients serving as diagnostic biomarkers in post-neurosurgical bacterial meningitis.Scientific reports · 2025Article
- Pharmacologic depletion of border-associated macrophages worsens disease in a mouse model of meningitis.Acta neuropathologica communications · 2025Article
- Cerebrospinal fluid quantitative proteomic reveals potential mechanisms and biomarker candidates of children with bacterial meningitis complicated by neurological complications.Clinical proteomics · 2025Article
- Glucose and Oxygen Levels Modulate the Pore-Forming Effects of Cholesterol-Dependent Cytolysin Pneumolysin fromToxins · 2024Article
- Cholesterol dependent cytolysins and the brain: Revealing a potential therapeutic avenue for bacterial meningitis.AIMS microbiology · 2023Review
- Bacterial meningitis-induced demyelination: A logical fallacy or groundbreaking avenue in neuroscience?AIMS neuroscience · 2023Article
- Saikosaponin D exerts antidepressant effect by regulating Homer1-mGluR5 and mTOR signaling in a rat model of chronic unpredictable mild stress.Chinese medicine · 2022Article
- Increased levels of the synaptic proteins PSD-95, SNAP-25, and neurogranin in the cerebrospinal fluid of patients with Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- Dendritic spine loss deep in the neocortex and dendrite distortion with diffusion disturbances occur early in experimental pneumococcal meningitis.Frontiers in neuroscience · 2022Article
- Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis.PLoS pathogens · 2020Article
- Interaction of Macrophages and Cholesterol-Dependent Cytolysins: The Impact on Immune Response and Cellular Survival.Toxins · 2020Review
- Derivation of a metabolic signature associated with bacterial meningitis in infants.Pediatric research · 2020Article
- Calbindin Deficits May Underlie Dissociable Effects of 5-HTMolecular neurobiology · 2020Article
- CSF Levels of Elongation Factor Tu Is Associated With Increased Mortality in Malawian Adults WithFrontiers in cellular and infection microbiology · 2020Article
- In vivo proteomics identifies the competence regulon and AliB oligopeptide transporter as pathogenic factors in pneumococcal meningitis.PLoS pathogens · 2019Article
- Pneumolysin and the bacterial capsule of Streptococcus pneumoniae cooperatively inhibit taxis and motility of microglia.Journal of neuroinflammation · 2019Article
- Intracellular ion and protein nanoparticle-induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli.Redox biology · 2019Article
- Cholesterol-Dependent Cytolysins Produced by Vaginal Bacteria: Certainties and Controversies.Frontiers in cellular and infection microbiology · 2019Review
- Characterization of Brain Dysfunction Induced by Bacterial Lipopeptides That Alter Neuronal Activity and Network in Rodent Brains.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Streptococcus pneumoniae (pneumococcal) meningitis is a common bacterial infection of the brain. The cholesterol-dependent cytolysin pneumolysin represents a key factor, determining the neuropathogenic potential of the pneumococci. Here, we demonstrate selective synaptic loss within the superficial layers of the frontal neocortex of post-mortem brain samples from individuals with pneumococcal meningitis. A similar effect was observed in mice with pneumococcal meningitis only when the bacteria expressed the pore-forming cholesterol-dependent cytolysin pneumolysin. Exposure of acute mouse brain slices to only pore-competent pneumolysin at disease-relevant, non-lytic concentrations caused permanent dendritic swelling, dendritic spine elimination and synaptic loss. The NMDA glutamate receptor antagonists MK801 and D-AP5 reduced this pathology. Pneumolysin increased glutamate levels within the mouse brain slices. In mouse astrocytes, pneumolysin initiated the release of glutamate in a calcium-dependent manner. We propose that pneumolysin plays a significant synapto- and dendritotoxic role in pneumococcal meningitis by initiating glutamate release from astrocytes, leading to subsequent glutamate-dependent synaptic damage. We outline for the first time the occurrence of synaptic pathology in pneumococcal meningitis and demonstrate that a bacterial cytolysin can dysregulate the control of glutamate in the brain, inducing excitotoxic damage.
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