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Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
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Pore-forming activity of clostridial binary toxins
O Knapp1, R Benz2, M R Popoff1
1Bactéries anaérobies et Toxines, Institut Pasteur, 28 rue du Dr Roux, Paris, France.
Biochimica Et Biophysica Acta
|August 18, 2015
Summary
Clostridial binary toxins utilize binding components to enter cells and disrupt the actin cytoskeleton, causing enteric diseases. Their pore-forming activity resembles heptameric pore-forming toxins.
Area of Science:
- Microbiology
- Toxicology
- Cell Biology
Background:
- Clostridial binary toxins, including Iota toxin and C2 toxin, are secreted by bacteria and consist of two protein components.
- These toxins disrupt the actin cytoskeleton via mono-ADP-ribosylation, leading to cellular damage and enteric diseases.
- Both clostridial and Bacillus binary toxins share structurally similar binding components responsible for cell entry.
Purpose of the Study:
- To compare the pore-forming activity of clostridial binary toxins with other related pore-forming toxins (PFTs).
- To elucidate the mechanism of cell internalization and cytosol transport mediated by the binding components of binary toxins.
Main Methods:
- Comparative analysis of structural and functional properties of binary toxin binding components.
- Review of existing literature on pore-forming toxins, including cholesterol-dependent cytotoxins and heptameric PFTs.
- Examination of the mechanism of actin cytoskeleton disruption by binary toxins.
Main Results:
- Clostridial and Bacillus binary toxins share conserved binding components that mediate receptor recognition, oligomerization, pore formation in endocytic vesicles, and enzymatic component transport.
- The binding components of binary toxins share structural similarities with pore-forming toxins (PFTs) like perfringolysin.
- The pore-forming activity of clostridial binding components is more analogous to heptameric PFTs, such as aerolysin and Clostridium perfringens epsilon toxin.
Conclusions:
- Clostridial binary toxins exhibit unique pore-forming characteristics distinct from cholesterol-dependent cytotoxins but related to heptameric PFTs.
- Understanding these pore-forming activities is crucial for comprehending the pathogenesis of clostridial binary toxins in enteric diseases.
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