ArticleThe Journal of clinical investigation2012
Identification of a novel pneumococcal vaccine antigen preferentially expressed during meningitis in mice.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Osmotic therapies added to antibiotics for acute bacterial meningitis.The Cochrane database of systematic reviews · 2018Pooled it
- Osmotic therapies added to antibiotics for acute bacterial meningitis.The Cochrane database of systematic reviews · 2013Pooled it
- Future Pneumococcal Vaccines: Shifting from Capsular Polysaccharides to Protein-Based Immunogens.Vaccines · 2026Review
- Breaking the fortress: a mechanistic review of meningitis-causing bacteria breaching tactics in blood brain barrier.Cell communication and signaling : CCS · 2025Review
- Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence ofmBio · 2024Article
- Differences in genetic flux in invasiveHeliyon · 2022Article
- Review
- Pyruvate Oxidase as a Key Determinant of Pneumococcal Viability during Transcytosis across Brain Endothelium.Journal of bacteriology · 2021Article
- The identification of co-expressed gene modules in Streptococcus pneumonia from colonization to infection to predict novel potential virulence genes.BMC microbiology · 2020Article
- Virulence Factors of Meningitis-Causing Bacteria: Enabling Brain Entry across the Blood-Brain Barrier.International journal of molecular sciences · 2019Review
- A Cross-Reactive Protein Vaccine Combined with PCV-13 Prevents Streptococcus pneumoniae- and Haemophilus influenzae-Mediated Acute Otitis Media.Infection and immunity · 2019Article
- Metformin mediates neuroprotection and attenuates hearing loss in experimental pneumococcal meningitis.Journal of neuroinflammation · 2019Article
- Streptococcus pneumoniae Cell Wall-Localized Trigger Factor Elicits a Protective Immune Response and Contributes to Bacterial Adhesion to the Host.Scientific reports · 2019Article
- Serotype-Independent Protection Against Invasive Pneumococcal Infections Conferred by Live Vaccine WithFrontiers in immunology · 2019Article
- Streptococcus pneumoniae: transmission, colonization and invasion.Nature reviews. Microbiology · 2018Review
- A recombinant conjugated pneumococcal vaccine that protects against murine infections with a similar efficacy to Prevnar-13.NPJ vaccines · 2018Article
- Intranasal Vaccination With Lipoproteins Confers Protection Against Pneumococcal Colonisation.Frontiers in immunology · 2018Article
- The Pneumococcal Alpha-Glycerophosphate Oxidase Enhances Nasopharyngeal Colonization through Binding to Host Glycoconjugates.EBioMedicine · 2017Article
- IQGAP1 Mediates Hcp1-PromotedFrontiers in cellular and infection microbiology · 2017Article
- Directed vaccination against pneumococcal disease.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Streptococcus pneumoniae is the most common cause of severe bacterial meningitis in children, the elderly, and immunocompromised individuals. To identify virulence factors preferentially expressed during meningitis, we conducted niche-specific genome-wide in vivo transcriptomic analysis after intranasal infection of mice with serotype 4 or 6A pneumococci. The expression of 34 bacterial genes was substantially altered in brain tissue of mice infected with either of the 2 strains. Ten upregulated genes were common to both strains, 7 of which were evaluated for their role in the development of meningitis. One previously uncharacterized protein, α-glycerophosphate oxidase (GlpO), was cytotoxic for human brain microvascular endothelial cells (HBMECs) via generation of H(2)O(2). A glpO deletion mutant was defective in adherence to HBMECs in vitro as well as in progression from the blood to the brain in vivo. Mutant bacteria also induced markedly reduced meningeal inflammation and brain pathology compared with wild type, despite similar levels of bacteremia. Immunization of mice with GlpO protected against invasive pneumococcal disease and provided additive protection when formulated with pneumolysin toxoid. Our results provide the basis of a strategy that can be adapted to identify genes that contribute to the development of meningitis caused by other pathogens.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.