ArticleProceedings of the National Academy of Sciences of the United States of America2015
Streptococcus pneumoniae secretes hydrogen peroxide leading to DNA damage and apoptosis in lung cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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
78 citing papers in PubMed, 139 citations in OpenAlex.
- Lactate Oxidase (LctO) Acts as a Metabolic Checkpoint RestrainingbioRxiv : the preprint server for biology · 2026Article
- Eliminate pneumococcal colonization by targeting intracellular acidification that promotes H2O2 production to enhance bacterial survival.PLoS pathogens · 2026Article
- Multi-Omics Reveal the Potential Associations ofJournal of inflammation research · 2026Article
- Article
- Stem cell-derived brain-like endothelial cells to interrogateVirulence · 2025Article
- Heme-mediated selection of encapsulatedEmerging microbes & infections · 2025Article
- Role of Atypical MAPK p38 Signaling in the Progression of Influenza A-Induced Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Pneumococcal HbioRxiv : the preprint server for biology · 2025Article
- Alleviating penicillin-resistant Streptococcus pneumoniae‑induced lung epithelial cell injury: mechanistic insights into effects of the optimized combination of main components from Yinhuapinggan granules.BMC infectious diseases · 2025Article
- Understanding the mechanisms ofTissue barriers · 2025Review
- The Mitochondrial Distribution and Morphology Family 33 GeneJournal of fungi (Basel, Switzerland) · 2024Article
- Oxidation of hemoproteins byMicrobiology spectrum · 2024Article
- Pneumococcal hydrogen peroxide regulates host cell kinase activity.Frontiers in immunology · 2024Article
- 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
- The role of pneumococcal extracellular vesicles on the pathophysiology of the kidney disease hemolytic uremic syndrome.mSphere · 2023Article
- Streptococcus pneumoniae disrupts the structure of the golgi apparatus and subsequent epithelial cytokine response in an HCell communication and signaling : CCS · 2023Article
- Bacterial and viral etiology of acute respiratory infection among the Forcibly Displaced Myanmar Nationals (FDMNs) in fragile settings in Cox's Bazar- a prospective case-control study.PLoS neglected tropical diseases · 2023Article
- Acute organ injury and long-term sequelae of severe pneumococcal infections.Pneumonia (Nathan Qld.) · 2023Review
- Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Streptococcus pneumoniae is a leading cause of pneumonia and one of the most common causes of death globally. The impact of S. pneumoniae on host molecular processes that lead to detrimental pulmonary consequences is not fully understood. Here, we show that S. pneumoniae induces toxic DNA double-strand breaks (DSBs) in human alveolar epithelial cells, as indicated by ataxia telangiectasia mutated kinase (ATM)-dependent phosphorylation of histone H2AX and colocalization with p53-binding protein (53BP1). Furthermore, results show that DNA damage occurs in a bacterial contact-independent fashion and that Streptococcus pyruvate oxidase (SpxB), which enables synthesis of H2O2, plays a critical role in inducing DSBs. The extent of DNA damage correlates with the extent of apoptosis, and DNA damage precedes apoptosis, which is consistent with the time required for execution of apoptosis. Furthermore, addition of catalase, which neutralizes H2O2, greatly suppresses S. pneumoniae-induced DNA damage and apoptosis. Importantly, S. pneumoniae induces DSBs in the lungs of animals with acute pneumonia, and H2O2 production by S. pneumoniae in vivo contributes to its genotoxicity and virulence. One of the major DSBs repair pathways is nonhomologous end joining for which Ku70/80 is essential for repair. We find that deficiency of Ku80 causes an increase in the levels of DSBs and apoptosis, underscoring the importance of DNA repair in preventing S. pneumoniae-induced genotoxicity. Taken together, this study shows that S. pneumoniae-induced damage to the host cell genome exacerbates its toxicity and pathogenesis, making DNA repair a potentially important susceptibility factor in people who suffer from pneumonia.
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.