A5027621740- Botulinum Toxin and Related Neurological Disorders
- Neurological disorders and treatments
- Hereditary Neurological Disorders
- Clostridium difficile and Clostridium perfringens research
- Streptococcal Infections and Treatments
- Biochemical and Structural Characterization
- Toxin Mechanisms and Immunotoxins
- Escherichia coli research studies
- Gut microbiota and health
- Lipid Membrane Structure and Behavior
- 3D Printing in Biomedical Research
- Pluripotent Stem Cells Research
- Plant-based Medicinal Research
- Antimicrobial Resistance in Staphylococcus
- Endoplasmic Reticulum Stress and Disease
- Helicobacter pylori-related gastroenterology studies
- Glycosylation and Glycoproteins Research
- Tissue Engineering and Regenerative Medicine
- Genetic Neurodegenerative Diseases
- Probiotics and Fermented Foods
- Bacteriophages and microbial interactions
- Microbial Metabolism and Applications
- Gastrointestinal motility and disorders
- Plant Pathogenic Bacteria Studies
- Sympathectomy and Hyperhidrosis Treatments
Kanazawa University
2016-2024
Osaka University
2007-2018
Kyushu University
2011
Kurume University
2010
Okayama University
1996-2005
University of Miyazaki
2005
Harvard University
2001-2004
Japan Science and Technology Agency
2004
Saitama Prefecture
2003
Boston Children's Hospital
2001-2002
Cholera toxin (CT) travels from the plasma membrane of intestinal cells to endoplasmic reticulum (ER) where a portion A-subunit, A1 chain, crosses into cytosol cause disease. A related toxin, LTIIb, binds but does not toxicity. Here, we show that B-subunit CT serves as carrier for A-subunit ER disassembly occurs. The gangliosides in lipid rafts and with ganglioside ER. In many cells, LTIIb follows similar pathway, human it fails associate is sorted away retrograde pathway Our results explain...
The molecular composition of progenitor toxins produced by a Clostridium botulinum type A strain (A-NIH) was analyzed. three types (19 S, 16 and 12 S) as reported previously. Purified 19 S demonstrated the same banding profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), indicating that they consist protein components. nontoxic components are non-hemagglutinin (HA) (molecular mass, 120 kDa) HA. HA could be fractionated into five subcomponents with masses 52, 35,...
Recent metagenomic analyses have revealed dysbiosis of the gut microbiota ulcerative colitis (UC) patients. However, impacts this are not fully understood, particularly at strain level.We perform whole-genome shotgun sequencing fecal DNA extracts from 13 healthy donors and 16 UC 8 Crohn's disease (CD) The CD patients is taxonomically functionally divergent that donors, with E. faecium being most differentially abundant species between two microbial communities. Transplantation feces or into...
Binding of the purified type C 7S (neurotoxin), 12S and 16S botulinum toxins to epithelial cells ligated small intestine or colon guinea pig (in vivo test) pre-fixed gastrointestinal tissue sections vitro was analysed. The toxin bound intensely microvilli in both tests, but did not bind stomach colon. neurotoxin Absorption assessed by determining titre sera pigs 6-8 h after intra-intestinal administration toxins. When [1 x 10(5) minimum lethal dose (MLD)] injected, 200-660 MLD ml-1 detected...
Botulinum neurotoxins (BoNTXs) produced by Clostridium botulinum are among the most poisonous substances known. Of seven types of BoNTXs, genes for type C1 and D toxins (BoNTX/C1 D) carried bacteriophages. The gene exoenzyme C3 also resides on these phages. Here, we present complete genome sequence c-st, a representative BoNTX/C1-converting is linear double-stranded DNA 185,682 bp with 404-bp terminal direct repeats, largest known temperate phage genome. We identified 198 potential...
Botulinum neurotoxin is produced by Clostridium botulinum and forms large protein complexes through associations with nontoxic components. We recently found that hemagglutinin (HA), one of the components, disrupts intercellular epithelial barrier; however, mechanism underlying this phenomenon not known. In study, we identified cadherin (E-cadherin) as a target molecule for HA. HA directly binds E-cadherin E-cadherin–mediated cell to adhesion. Although human, bovine, mouse E-cadherin, it does...
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...
ABSTRACT Botulinum neurotoxins (BoNTs) are a class of toxins produced by Clostridium botulinum ( C. ) and other species Clostridia . BoNT/X is putative novel neurotoxin identified through genome sequencing capable SNARE cleavage, but its neurotoxic potential in humans vertebrates remained unclear. The strain producing BoNT/X, Strain 111, encodes both plasmid-borne bont/b2 as well the chromosomal bont/x This study utilized 111 from Japan recombinantly full-length to more fully analyze this...
Clostridium botulinum type A hemagglutinin‐positive progenitor toxin consists of three distinct components: neurotoxin (NTX), hemagglutinin (HA), and non‐toxic non‐HA (NTNH). The HA four subcomponents designated HA1, 2, 3a 3b. By employing purified GST‐fusion proteins each subcomponent, we found that the HA‐positive toxin, GST‐HA1 GST‐HA3b bind to human erythrocytes microvilli guinea pig upper small intestinal sections. via galactose moieties, binds sialic acid moieties. GST‐2 GST‐3a showed...
The type B botulinum neurotoxin (BoNT) elicits flaccid paralysis and death in humans by intoxicating peripheral nerves after oral absorption. Here, we examine the function of haemagglutinin (HA), a non-toxic component large 16S BoNT complex. We find that HA acts intestine to disrupt epithelial barrier opening intercellular tight adherens junctions. This allows transport other solutes into systemic circulation explains how complexes are efficiently absorbed. In vitro, appears act on cell via...
Cholera toxin (CT) and related AB 5 toxins bind to glycolipids at the plasma membrane are then transported in a retrograde manner, first Golgi endoplasmic reticulum (ER). In ER, catalytic subunit of CT is translocated into cytosol, resulting toxicity. Using fluorescence microscopy, we found that internalized by multiple endocytic pathways. Inhibition clathrin-, caveolin-, or Arf6-dependent pathways overexpression appropriate dominant mutants had no effect on traffic it did not affect...
Orally ingested botulinum neurotoxin (BoNT) causes food-borne botulism, but BoNT must pass through the gut lining and enter bloodstream. We have previously found that type B haemagglutinin (HA) proteins in toxin complex play an important role intestinal absorption of by disrupting paracellular barrier epithelium, therefore facilitating transepithelial delivery BoNT. Here, we show A HA a similar disruptive activity greater potency than human epithelial cell lines Caco-2 T84 canine kidney line...
A polymerase chain reaction (PCR)-based method was established to detect each type of neurotoxin genes Clostridium botulinum types F by employing the oligonucleotide primer sets corresponding special regions light chains neurotoxins. In this procedure, PCR products were easily confirmed restriction enzyme digestion profiles, and as little 2.5 pg template DNAs from toxigenic strains could be detected. The specific obtained C. F, a E toxin-producing butyricum strain, baratii but no product...
AbstractClostridium botulinum strains produce seven immunologically distinct neurotoxins (NTX), type A to G. the NTXs associate with nontoxic components in cultures, and become large complexes three forms (12S, 16S, 19S) designated progenitor toxins. 12S toxin consists of a NTX component having no hemagglutinin (HA) activity (described here as non-toxic non-HA, NTNH), 16S 19S toxins are formed by conjugation HA. Based on genetic-and protein chemical-analyses it became clear that 1) HA four...
The genes of the botulinum neurotoxin A (BoNT) complex are clustered in a locus consisting two divergent polycistronic operons, one containing non‐toxic, non‐haemagglutinin (NTNH) component and bontA genes, other haemagglutinin (HA) genes. operons separated by gene ( botR/A , previously called orf 21) encoding 21 kDa protein. recombinant Clostridium strain that overexpresses was constructed electroporating 62 with vector pAT19 under control its own promoter. transformed produced more BoNT/A...
Clostridium botulinum type C 16S progenitor toxin consists of a neurotoxin (NTX), non-toxic non-HA (NTNH), and haemagglutinin (HA). The HA acts as an adhesin, allowing the to bind intestinal epithelial cells erythrocytes. In C, these bindings are dependent on sialic acid. four distinct subcomponents designated HA1, HA2, HA3a HA3b. To identify binding subcomponent(s) toxin, all HA-subcomponents some their precursor forms were produced recombinant proteins fused glutathione S-transferase...