ArticlePLoS pathogens2012
DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 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
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Presence of Group A streptococcus frequently assayed virulence genes in invasive disease: a systematic review and meta-analysis.Frontiers in cellular and infection microbiology · 2024Pooled it
- Molecular mechanism of complement interference by Streptococcus pyogenes nuclease A.Communications biology · 2026Article
- Neutrophil Extracellular Traps and Complement Pathways: The Missing Links in Acute Rheumatic Fever and Rheumatic Heart Disease Pathogenesis.Journal of cardiovascular translational research · 2026Review
- Group A Streptococcal Virulence Factors and Vaccine Development-An Update.Microorganisms · 2026Review
- Host-response trajectories in necrotizing fasciitis: host-pathogen interactions, immune evasion, and immunoparalysis.Frontiers in cellular and infection microbiology · 2026Review
- Staphylococcus aureus thermonuclease NucA is a key virulence factor in septic arthritis.Communications biology · 2025Article
- Comparison of pharyngeal and invasive isolates ofMicrobiology spectrum · 2025Article
- The burden of group AiScience · 2025Review
- Global spread of Streptococcus pyogenes A genomics-supported narrative review.FEMS microbiology reviews · 2025Review
- The intricate pathogenicity of Group AVirulence · 2024Review
- Evaluation of Probiotic Potential and Functional Properties ofFoods (Basel, Switzerland) · 2024Article
- Nosocomial Transmission of Necrotizing Fasciitis: A Molecular Characterization of Group A Streptococcal DNases in Clinical Virulence.Microorganisms · 2024Article
- Review
- Group A Streptococcus strains causing meningitis without distinct invasive phenotype.MicrobiologyOpen · 2024Article
- Group A Streptococcal Collagen-like Protein 1 Restricts Tumor Growth in Murine Pancreatic Adenocarcinoma and Inhibits Cancer-Promoting Neutrophil Extracellular Traps.bioRxiv : the preprint server for biology · 2024Article
- Immunomodulating Enzymes fromMicroorganisms · 2024Review
- Group A streptococcal collagen-like protein 1 restricts tumor growth in murine pancreatic adenocarcinoma and inhibits cancer-promoting neutrophil extracellular traps.Frontiers in immunology · 2024Article
- Pathogenesis, epidemiology and control of Group A Streptococcus infection.Nature reviews. Microbiology · 2023Review
- Emerging applications of cancer bacteriotherapy towards treatment of pancreatic cancer.Frontiers in oncology · 2023Review
- Immunity to Sda1 Protects against Infection by Sda1Vaccines · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Group A Streptococcus (GAS) has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase.
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.