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Enrichment and Detection of Clostridium perfringens Toxinotypes in Retail Food Samples
Published on: October 18, 2019
Identification and structural characterization of anthrax toxin receptor 2 as the Clostridium perfringens NetF
Chang Wang1,2, Filippo Cattalani2,3, Ioan Iacovache1
1Institute of Anatomy, University of Bern, Bern, Switzerland.
Abstract:
Hemolysin β-pore-forming toxins (βPFTs) are key virulence factors of Clostridium perfringens, associated with severe diseases in humans and animals. Yet, the mechanisms by which Clostridium βPFTs recognize and engage specific target cells remain poorly understood. Here, we identify the cellular receptor for C. perfringens necrotizing enteritis toxin F (NetF), a recently discovered toxin implicated in severe enteritis in dogs and foals. We show that NetF binds to the same receptor as anthrax toxin, namely ANTXR2. Using cryo-electron microscopy, we determined the structure of the oligomeric NetF pre-pore as well as the transmembrane pore, both alone and in complex with the extracellular domain of ANTXR2. Unlike anthrax toxin, which binds to the apical MIDAS motif of ANTXR2 - as does the natural ANTXR2 ligand collagen type VI - NetF engages the receptor laterally, spanning both the von Willebrand A and the Ig-like domains. This interaction positions the toxin near the membrane, facilitating contact with membrane lipids and promoting transmembrane pore formation. Our findings uncover key principles of hemolysin βPFT-receptor recognition and advance our understanding of how pathogenic bacteria use these toxins to breach host defenses.
Insights
Clostridium perfringens necrotizing enteritis toxin F (NetF) binds to ANTXR2, the same receptor as anthrax toxin. This toxin uses a unique lateral binding mechanism to form pores, unlike anthrax toxin's apical binding.
Area of Science:
- Microbiology
- Structural Biology
- Toxicology
Background:
- Hemolysin β-pore-forming toxins (βPFTs) are critical virulence factors in Clostridium perfringens, causing severe diseases.
- The precise mechanisms by which Clostridium βPFTs target specific host cells are not well understood.
Purpose of the Study:
- To identify the cellular receptor for Clostridium perfringens necrotizing enteritis toxin F (NetF).
- To elucidate the structural basis of NetF-receptor interaction and pore formation.
Main Methods:
- Utilized cryo-electron microscopy to determine the structures of NetF pre-pore and pore complexes.
- Investigated the interaction between NetF and the extracellular domain of its identified receptor, ANTXR2.
Main Results:
- Identified ANTXR2 as the cellular receptor for NetF, the same receptor targeted by anthrax toxin.
- Determined that NetF binds laterally to ANTXR2, engaging both von Willebrand A and Ig-like domains, distinct from anthrax toxin's apical binding.
- Structural analysis revealed how NetF's lateral interaction facilitates membrane lipid contact and pore formation.
Conclusions:
- NetF employs a novel lateral binding mechanism to ANTXR2 for host cell invasion.
- Findings provide crucial insights into βPFT-receptor recognition and bacterial toxin mechanisms.
- Advances understanding of how pathogenic bacteria breach host defenses using toxins.
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