A5011472188- Botulinum Toxin and Related Neurological Disorders
- Neurological disorders and treatments
- Hereditary Neurological Disorders
- Streptococcal Infections and Treatments
- Toxin Mechanisms and Immunotoxins
- Plant-based Medicinal Research
- Wnt/β-catenin signaling in development and cancer
- Cancer Treatment and Pharmacology
- Periodontal Regeneration and Treatments
- Biochemical and Structural Characterization
- Reconstructive Surgery and Microvascular Techniques
- Blood disorders and treatments
- Tissue Engineering and Regenerative Medicine
- Laser Applications in Dentistry and Medicine
- Clostridium difficile and Clostridium perfringens research
- Bacterial Infections and Vaccines
Kanazawa University
2016-2024
Osaka University
2014-2015
Kyoto Institute of Technology
2013
Abstract To cause food-borne botulism, botulinum neurotoxin (BoNT) in the gastrointestinal lumen must traverse intestinal epithelial barrier. However, mechanism by which BoNT crosses barrier remains unclear. BoNTs are produced along with one or more non-toxic components, they form progenitor toxin complexes (PTCs). Here we show that serotype A1 L-PTC, has high oral toxicity and makes predominant contribution to causing illness, breaches from microfold (M) cells via an interaction between...
Botulinum neurotoxin (BoNT) inhibits neurotransmitter release in motor nerve endings, causing botulism, a condition often resulting from ingestion of the toxin or toxin-producing bacteria. BoNTs are always produced as large protein complexes by associating with non-toxic protein, non-hemagglutinin (NTNH), and some contain another hemagglutinin (HA), addition to NTNH. These accessory proteins known increase oral toxicity dramatically. NTNH has protective role against harsh conditions...
Botulinum neurotoxin is conventionally divided into seven serotypes, designated A-G, and produced as large protein complexes through associations with non-toxic components, such hemagglutinin (HA) non-HA. These proteins dramatically enhance the oral toxicity of toxin complex. HA considered to have a role in transport intestinal epithelium by carbohydrate binding epithelial barrier-disrupting activity. Type A B HAs disrupt E-cadherin-mediated cell adhesion, and, turn, intercellular barrier. C...
Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of botulism requires development effective toxin-neutralizing antibodies without side effects such as serum sickness anaphylaxis. In this study, we generated fully monoclonal (HuMAbs) against serotype B (BoNT/B1) using a murine–human chimera fusion partner cell line named SPYMEG. these HuMAbs, M2, which specifically binds light chain...
Clostridium botulinum produces neurotoxin complexes that cause botulism. Previous studies elucidated the molecular pathogenesis of complexes; however, it currently remains unclear whether other components bacterium affect host cells. Recent provided insights into role bacterial membrane vesicles (MVs) produced by some species in immunity and pathology. We herein examined compared cellular effects MVs isolated from four strains C. with those closely related sporogenes two symbiont scindens....
Hemagglutinin (HA) is one of the components botulinum neurotoxin (BoNT) complexes and it promotes absorption BoNT through intestinal epithelium by at least two specific mechanisms: cell surface attachment carbohydrate binding, epithelial barrier disruption E-cadherin binding. It known that HA forms a three-arm structure, in which each three protomers has carbohydrate-binding sites E-cadherin-binding site. A form considered to bind these ligands simultaneously. In present study, we...
Abstract Clostridium botulinum causes the disease botulism, and nontoxigenic sporogenes is closely related to group I C. botulinum. Despite its pathogenicity, remains poorly characterized. Genetic manipulation critical for understanding bacterial physiology disease. We compared conjugal transformation efficiencies of seven strains, including (strains 62A, 7I03-H, Okra, Osaka05, 111) JCM 1416 T , ATCC 15579), our results showed that few or no transformants were obtained in certain strains. In...
Abstract Botulism is a deadly neuroparalytic condition caused by the botulinum neurotoxin (BoNT) produced Clostridium and related species. Toxin‐neutralizing antibodies are most effective treatments for BoNT intoxication. We generated human monoclonal neutralizing type B (BoNT/B), designated M2 M4. The combination of these exhibited strong effect against BoNT/B toxicity. In this study, we analyzed mechanisms action in vitro. M4 binds to C‐terminus heavy chain (the receptor‐binding domain)...
Hemagglutinin (HA), a nontoxic component of the botulinum neurotoxin (BoNT) complex, binds to E-cadherin and inhibits E-cadherin-mediated cell–cell adhesion. HA is 470 kDa protein complex comprising six HA1, three HA2, HA3 subcomponents. Thus, prepare recombinant full-length in vitro, it necessary reconstitute macromolecular from purified subcomponents, which involves multiple purification steps. In this study, we developed NanoHA, minimal inhibitor derived Clostridium with simple strategy...
ABSTRACT Botulinum neurotoxin (BoNT) is the most potent natural toxin known. Of seven BoNT serotypes (A to G), types A, B, E, and F cause human botulism. Treatment of botulism requires development effective toxin-neutralizing antibodies without side effects such as serum sickness anaphylaxis. In this study, we generated fully monoclonal (HuMAbs) against serotype B (BoNT/B1) using a murine–human chimera fusion partner cell line named SPYMEG. these HuMAbs, M2, which specifically binds light...
Botulinum neurotoxins (BoNTs), which are produced by Clostridium botulinum, the most potent toxins, and cause highly lethal food poisoning. BoNTs as assemblies with non-toxic components. Hemagglutinin (HA), one of components, has three biological activities: is protecting BoNT from degradation in gastrointestinal tract, another binding activity to carbohydrates other disrupting epithelial barrier direct E-cadherin, critical for oral toxicity BoNT. Here, we review study on crystal structure...