ArticlePLoS pathogens2015
The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ε-Toxin.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
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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.
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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.
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Who cites it
60 citing papers in PubMed, 89 citations in OpenAlex.
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- Microbial-Immune Interplay in CNS Autoimmune Diseases: Lessons from Animal Models and Clinical Studies.European journal of immunology · 2026Review
- ThemBio · 2025Article
- Milestones in Clostridium perfringens research since 1995.Anaerobe · 2025Review
- Potential mechanisms linking bacterial factors to the development and progression of multiple sclerosis.Infectious medicine · 2025Review
- Does Clostridium Perfringens Epsilon Toxin Mimic an Auto-Antigen Involved in Multiple Sclerosis?Toxins · 2025Observational
- Effect ofNAM journal · 2025Article
- Intestinal pathology in goats challenged withVeterinary pathology · 2025Article
- Epsilon Toxin fromToxins · 2024Article
- The epsilon toxin from Clostridium perfringens stimulates calcium-activated chloride channels, generating extracellular vesicles in Xenopus oocytes.Pharmacology research & perspectives · 2024Article
- Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution.Toxins · 2024Review
- The Molecular Architecture and Mode of Action ofToxins · 2024Review
- Review
- IsMultiple sclerosis (Houndmills, Basingstoke, England) · 2023Review
- Tissue Washing Improves Native Ambient Mass Spectrometry Detection of Membrane Proteins Directly from Tissue.Journal of the American Chemical Society · 2023Article
- Article
- Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.The Journal of clinical investigation · 2023Article
- Systematic evaluation of membrane-camouflaged nanoparticles in neutralizing Clostridium perfringens ε-toxin.Journal of nanobiotechnology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity.
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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.