ArticleNature medicine2016
Activation of Bacteroides fragilis toxin by a novel bacterial protease contributes to anaerobic sepsis in mice.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Gut Microbiota Dysbiosis and Neuroinflammation in Alzheimer's Disease: a Systematic Review of Mechanistic Insights.Molecular neurobiology · 2026Pooled it
- Bacteroides fragilis toxin promotes gall bladder cancer in mice.Nature microbiology · 2026Article
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- Orally available designed miniproteins inhibit enterotoxigenicbioRxiv : the preprint server for biology · 2026Article
- An ubiquitous antibacterial toxin from human gut bacteria engenders neonatal colonization advantage.Nature communications · 2026Article
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- Biosynthesis, Structure, and Antibiotic Properties of Gelatinamin A, a Triculamin-Like Lasso Peptide.Chembiochem : a European journal of chemical biology · 2026Article
- The "Direct Structural Disruption" Hypothesis:Toxins · 2026Review
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- Acupuncture: A Promising Non-Pharmacological Approach to Parkinson's Disease Management.Brain and behavior · 2026Review
- Current landscape and challenges in anaerobic bloodstream infections: epidemiology, microbiology, and clinical management.Frontiers in microbiology · 2026Review
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- Interbacterial warfare in the human gut: insights from Bacteroidales' perspective.Gut microbes · 2025Review
- Lessons from the model gut BacteroidalesJournal of bacteriology · 2025Review
- Cordycepin Mitigates Sepsis-Associated Encephalopathy by Promoting Microglial M2 Polarization via the IL-17a/IL-17RA/NF-κB Axis.Molecular neurobiology · 2025Article
- The Ambivalent Nature ofToxins · 2025Review
- A Bacteroides fragilis protease activates host PARCell host & microbe · 2025Article
- Environmental factors drive bacterial degradation of gastrointestinal mucus.NPJ biofilms and microbiomes · 2025Article
- Gut Microbiota Mediates Neuroinflammation in Alzheimer's Disease: Unraveling Key Factors and Mechanistic Insights.Molecular neurobiology · 2025Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Bacteroides fragilis is the leading cause of anaerobic bacteremia and sepsis. Enterotoxigenic strains that produce B. fragilis toxin (BFT, fragilysin) contribute to colitis and intestinal malignancy, yet are also isolated in bloodstream infection. It is not known whether these strains harbor unique genetic determinants that confer virulence in extra-intestinal disease. We demonstrate that BFT contributes to sepsis in mice, and we identify a B. fragilis protease called fragipain (Fpn) that is required for the endogenous activation of BFT through the removal of its auto-inhibitory prodomain. Structural analysis of Fpn reveals a His-Cys catalytic dyad that is characteristic of C11-family cysteine proteases that are conserved in multiple pathogenic Bacteroides spp. and Clostridium spp. Fpn-deficient, enterotoxigenic B. fragilis has an attenuated ability to induce sepsis in mice; however, Fpn is dispensable in B. fragilis colitis, wherein host proteases mediate BFT activation. Our findings define a role for B. fragilis enterotoxin and its activating protease in the pathogenesis of bloodstream infection, which indicates a greater complexity of cellular targeting and activity of BFT than previously recognized. The expression of fpn by both toxigenic and nontoxigenic strains suggests that this protease may contribute to anaerobic sepsis in ways that extend beyond its role in toxin activation. It could thus potentially serve as a target for disease modification.
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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.