ArticleScientific reports2016
Pneumococcal Pneumolysin Induces DNA Damage and Cell Cycle Arrest.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Pneumolysin as a target for new therapies against pneumococcal infections: A systematic review.PloS one · 2023Pooled it
- Bioengineered Extracellular Vesicles Mitigate Neuroinflammation by Neutralizing Pneumolysin and Delaying Disease Onset in Experimental Pneumococcal Meningitis.Journal of extracellular vesicles · 2026Article
- Computational identification of novel therapeutic candidates for Streptococcus pyogenes and influenza A coinfections through transcriptomic-based drug repositioning.BMC microbiology · 2026Article
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- A pro-carcinogenic oral microbe internalized by breast cancer cells promotes mammary tumorigenesis.Cell communication and signaling : CCS · 2026Article
- Pneumolysin-responsive liposomal platform for selective treatment of Streptococcus pneumoniae.Drug delivery and translational research · 2025Article
- Human Enterovirus D68 infection - the intricate dance of cells, genes, and invading bugs.Frontiers in cellular and infection microbiology · 2025Article
- Population genomics of Streptococcus mitis in UK and Ireland bloodstream infection and infective endocarditis cases.Nature communications · 2024Article
- Bacterial pore-forming toxin pneumolysin drives pathogenicity through host extracellular vesicles released during infection.iScience · 2024Article
- Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function.Disease models & mechanisms · 2024Article
- Article
- Review
- NADNature communications · 2023Article
- Impact of Endogenous Pneumococcal Hydrogen Peroxide on the Activity and Release of Pneumolysin.Toxins · 2023Article
- The choline-binding proteins PspA, PspC, and LytA ofInfection and immunity · 2023Article
- Modulation of innate immunity in airway epithelium for host-directed therapy.Frontiers in immunology · 2023Review
- Oral Microbiome in Nonsmoker Patients with Oral Cavity Squamous Cell Carcinoma, Defined by Metagenomic Shotgun Sequencing.Cancers · 2022Article
- Molecular Characterization of Predominant Serotypes, Drug Resistance, and Virulence Genes ofFrontiers in microbiology · 2022Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Streptococcus pneumoniae produces pneumolysin toxin as a key virulence factor against host cells. Pneumolysin is a cholesterol-dependent cytolysin (CDC) toxin that forms lytic pores in host membranes and mediates pneumococcal disease pathogenesis by modulating inflammatory responses. Here, we show that pneumolysin, which is released during bacterial lysis, induces DNA double strand breaks (DSBs), as indicated by ataxia telangiectasia mutated (ATM)-mediated H2AX phosphorylation (γH2AX). Pneumolysin-induced γH2AX foci recruit mediator of DNA damage checkpoint 1 (MDC1) and p53 binding protein 1 (53BP1), to sites of DSBs. Importantly, results show that toxin-induced DNA damage precedes cell cycle arrest and causes apoptosis when DNA-dependent protein kinase (DNA-PK)-mediated non-homologous end joining is inhibited. Further, we observe that cells that were undergoing DNA replication harbored DSBs in greater frequency during pneumolysin treatment. This observation raises the possibility that DSBs might be arising as a result of replication fork breakdown. Additionally, neutralizing the oligomerization domain of pneumolysin with monoclonal antibody suppresses DNA damage and also cell cycle arrest, indicating that pneumolysin oligomerization is important for causing DNA damage. Taken together, this study reveals a previously unidentified ability of pneumolysin to induce cytotoxicity via DNA damage, with implications in the pathophysiology of S. pneumoniae infection.
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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.