A5049731951- Clostridium difficile and Clostridium perfringens research
- Botulinum Toxin and Related Neurological Disorders
- Toxin Mechanisms and Immunotoxins
- Ginseng Biological Effects and Applications
- Pharmacological Effects of Natural Compounds
- Gut microbiota and health
- Bacillus and Francisella bacterial research
- Yersinia bacterium, plague, ectoparasites research
- Escherichia coli research studies
- Vagus Nerve Stimulation Research
- Erythrocyte Function and Pathophysiology
- Mycobacterium research and diagnosis
- Immune Response and Inflammation
- Genomics and Phylogenetic Studies
- Bacteriophages and microbial interactions
- Diphtheria, Corynebacterium, and Tetanus
- Genetics, Bioinformatics, and Biomedical Research
- Milk Quality and Mastitis in Dairy Cows
Rockefeller University
2010-2024
Cornell University
2013-2015
MIND Research Institute
2013-2015
Tri-Institutional PhD Program in Chemical Biology
2013
We have isolated Clostridium perfringens type B, an epsilon toxin-secreting bacillus, from a young woman at clinical presentation of Multiple Sclerosis (MS) with actively enhancing lesions on brain MRI. This finding represents the first time that C. B has been detected in human. Epsilon toxin's tropism for blood-brain barrier (BBB) and binding to oligodendrocytes/myelin makes it provocative candidate nascent lesion formation MS. examined well-characterized population MS patients healthy...
Multiple Sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis common in MS, but specifically causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection show that people with MS were more likely harbor greater abundance epsilon toxin (ETX)-producing strains C. perfringens within their gut microbiomes compared healthy controls (HC). patient-derived isolates produced functional ETX had...
Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes damage poorly understood. In this study, we sought to determine the molecular and cellular mechanisms pathological changes matter. primary CNS cultures, binds kills oligodendrocytes but not astrocytes, microglia, or neurons. cerebellar organotypic culture, induces demyelination, occurs time-...
Clostridium perfringens ε-toxin (ETX) is a potent pore-forming toxin responsible for 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 potential causative agent Multiple Sclerosis (MS), human that begins BBB breakdown injury to myelin forming cells the CNS. The receptor unknown. Here we show both binding mammalian cytotoxicity requires tetraspan proteolipid Myelin Lymphocyte...
There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two these medications, Fingolimod, and Teriflunomide, considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from gut bacterium, Clostridium perfringens, may initiate newly forming lesions due its tropism blood-brain barrier (BBB)...
Clostridium perfringens epsilon toxin (ETX) is the third most lethal bacterial and has been suggested to be an environmental trigger of multiple sclerosis, immune-mediated disease human central nervous system. However, ETX cytotoxicity on primary cells not investigated. In this article, we demonstrate that preferentially binds kills lymphocytes expressing increased levels myelin lymphocyte protein MAL. Using flow cytometry, binding was determined time dose dependent highest for CD4+ cells,...
On January 10th, 2024, Barrie et al. published a landmark paper identifying the ancestral European origin of high-risk, multiple sclerosis (MS) allele, HLA-DRB1*15:01. The authors hypothesize that Bronze Age, Yamnaya migration to, and their population Scandinavia British Isles, accounts for high incidence MS in these regions, stemming from geographical spread HLA-DRB1*15:01 as evidenced by data. These data further indicate this immune-related allele likely underwent positive-selection...
ABSTRACT During active multiple sclerosis (MS), red blood cells (RBCs) harvested from patients reportedly display increased osmotic fragility and cellular volume (macrocytosis). The cause of these abnormalities remains unknown. We have previously proposed that Clostridium perfringens epsilon toxin (ETX) may be a blood-borne trigger for newly forming MS lesions based on its tropism blood-brain barrier vasculature CNS myelin. Recently, Gao et al. reported ETX binds to damages human RBCs,...
Background: The earliest MS lesions exhibit oligodendrocyte apoptosis, BBB permeability, and early microglial activation with a conspicuous absence of infiltrating lymphocytes, arguing against beginning as an autoimmune phenomenon. We reasoned that the environmental trigger for initial lesion formation in might be soluble toxin based on these histopathologic features have identified Clostridium perfringens epsilon (ETX) candidate toxin. Methods: Stool specimens were self-collected by...