ArticleCommunications biology2020
A serine protease secreted from Bacillus subtilis cleaves human plasma transthyretin to generate an amyloidogenic fragment.
Article in Communications biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Gut-Heart Axis: Microbiome Involvement in Wild-Type Transthyretin Amyloidosis.International journal of molecular sciences · 2026Article
- Causal relationship of familial hypercholesterolemia with risk of intestinal vascular disorders: A mendelian randomization study.Metabolism open · 2025Article
- Gut-Heart Axis: Microbiome Involvement in Restrictive Cardiomyopathies.Biomedicines · 2025Review
- Protein hydrolysates fromTranslational animal science · 2025Article
- Knowledge Landscape and Hotspots of Research in Transthyretin Amyloid Cardiomyopathy: A Bibliometric Analysis.International journal of medical sciences · 2025Article
- Bioactive Peptides from Corn (Biology · 2024Review
- Chemical Synthesis and Structure-Activity Relationship Studies of the Coagulation Factor Xa Inhibitor Tick Anticoagulant Peptide from the Hematophagous ParasiteBiomimetics (Basel, Switzerland) · 2024Article
- Association between rat decompression sickness resistance, transthyretin single nucleotide polymorphism, and expression: A pilot study.Physiological reports · 2024Article
- Degradation versus fibrillogenesis, two alternative pathways modulated by seeds and glycosaminoglycans.Protein science : a publication of the Protein Society · 2024Article
- From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).Protein science : a publication of the Protein Society · 2023Article
- The Role of Proteolysis in Amyloidosis.International journal of molecular sciences · 2022Review
- Exogenous human α-Synuclein acts in vitro as a mild platelet antiaggregant inhibiting α-thrombin-induced platelet activation.Scientific reports · 2022Article
- Role of microbial secreted proteins in gut microbiota-host interactions.Frontiers in cellular and infection microbiology · 2022Review
- Current and Emerging Therapies for Hereditary Transthyretin Amyloidosis: Strides Towards a Brighter Future.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Aggregation-Prone Structural Ensembles of Transthyretin Collected With Regression Analysis for NMR Chemical Shift.Frontiers in molecular biosciences · 2021Article
- A conserved Neurite Outgrowth and Guidance motif with biomimetic potential in neuronal Cell Adhesion Molecules.Computational and structural biotechnology journal · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of human wild-type transthyretin (hTTR), a homo-tetrameric plasma protein, leads to acquired senile systemic amyloidosis (SSA), recently recognised as a major cause of cardiomyopathies in 1-3% older adults. Fragmented hTTR is the standard composition of amyloid deposits in SSA, but the protease(s) responsible for amyloidogenic fragments generation in vivo is(are) still elusive. Here, we show that subtilisin secreted from Bacillus subtilis, a gut microbiota commensal bacterium, translocates across a simulated intestinal epithelium and cleaves hTTR both in solution and human plasma, generating the amyloidogenic fragment hTTR(59-127), which is also found in SSA amyloids in vivo. To the best of our knowledge, these findings highlight a novel pathogenic mechanism for SSA whereby increased permeability of the gut mucosa, as often occurs in elderly people, allows subtilisin (and perhaps other yet unidentified bacterial proteases) to reach the bloodstream and trigger generation of hTTR fragments, acting as seeding nuclei for preferential amyloid fibrils deposition in the heart.
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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.