ArticlePLoS pathogens2018
Heterogeneity in pneumolysin expression governs the fate of Streptococcus pneumoniae during blood-brain barrier trafficking.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- LC3 forms functional nanoclusters on autophagosomes.EMBO reports · 2026Article
- Host AAA-ATPase VCP/p97 lyses ubiquitinated intracellular bacteria as an innate antimicrobial defence.Nature microbiology · 2025Article
- Understanding the mechanisms ofTissue barriers · 2025Review
- Molecular mechanisms of streptococcal disruption of the blood-brain barrier and their pathogenic role in bacterial meningitis.Frontiers in immunology · 2025Review
- Review
- Development of an inducer-free, virulence gene promoter-controlled, and fluorescent reporter-labeled CRISPR interference system inMicrobiology spectrum · 2024Article
- A 3'UTR-derived small RNA represses pneumolysin synthesis and facilitates pneumococcal brain invasion.Communications biology · 2024Article
- Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection.iScience · 2024Article
- Biological puzzles solved by usingJournal of bacteriology · 2024Review
- Article
- Pathogenic bacteria exploit transferrin receptor transcytosis to penetrate the blood-brain barrier.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.Science advances · 2023Article
- Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole-animal dual RNA-seq.Cell reports · 2022Article
- Differential Ubiquitination as an Effective Strategy Employed by the Blood-Brain Barrier for Prevention of Bacterial Transcytosis.Journal of bacteriology · 2022Article
- Review
- The Yin and Yang of Pneumolysin During Pneumococcal Infection.Frontiers in immunology · 2022Review
- Pyruvate Oxidase as a Key Determinant of Pneumococcal Viability during Transcytosis across Brain Endothelium.Journal of bacteriology · 2021Article
- Production ofFrontiers in cellular and infection microbiology · 2021Article
- Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis.PLoS pathogens · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Outcome of host-pathogen encounter is determined by the complex interplay between protective bacterial and host defense strategies. This complexity further amplifies with the existence of cell-to-cell phenotypic heterogeneity in pathogens which remains largely unexplored. In this study, we illustrated that heterogeneous expression of pneumolysin (Ply), a pore-forming toxin of the meningeal pathogen, S. pneumoniae (SPN) gives rise to stochastically different bacterial subpopulations with variable fate during passage across blood-brain barrier (BBB). We demonstrate that Ply mediated damage to pneumococcus containing vacuolar (PCV) membrane leads to recruitment of cytosolic "eat-me" signals, galectin-8 and ubiquitin, targeting SPN for autophagic clearance. However, a majority of high Ply producing subset extensively damages autophagosomes leading to pneumococcal escape into cytosol and efficient clearance by host ubiquitination machinery. Interestingly, a low Ply producing subset halts autophagosomal maturation and evades all intracellular defense mechanisms, promoting its prolonged survival and successful transcytosis across BBB, both in vitro and in vivo. Ply therefore acts as both, sword and shield implying that its smart regulation ensures optimal disease manifestation. Our elucidation of heterogeneity in Ply expression leading to disparate infection outcomes attempts to resolve the dubious role of Ply in pneumococcal pathogenesis.
Indexed as
Identifiers
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.