LIVIVO - Search results -

Search results

Result 1 - 10 of total 33

Search options

Article ; Online: Botulinum neurotoxin X lacks potency in mice and in human neurons.

Gregg, Brieana M / Matsumura, Takuhiro / Wentz, Travis G / Tepp, William H / Bradshaw, Marite / Stenmark, Pål / Johnson, Eric A / Fujinaga, Yukako / Pellett, Sabine

mBio

2024 Volume 15, Issue 3, Page(s) e0310623

Abstract: Botulinum neurotoxins (BoNTs) are a class of toxins produced by : Importance: The family of botulinum neurotoxins comprises the most potent toxins known to humankind. New members of this family of protein toxins as well as more distantly related ... ...

Abstract	Botulinum neurotoxins (BoNTs) are a class of toxins produced by Importance: The family of botulinum neurotoxins comprises the most potent toxins known to humankind. New members of this family of protein toxins as well as more distantly related homologs are being identified. The discovery of BoNT/X via bioinformatic screen in 2017 as a putative new BoNT serotype raised concern about its potential as a pathogenic agent with no available countermeasures. This study for the first time assessed both recombinantly produced and native purified BoNT/X for its vertebrate neurotoxicity.
MeSH term(s)	Humans ; Animals ; Mice ; Neurotoxins/chemistry ; Neurotoxins/genetics ; Neurotoxins/metabolism ; Clostridium botulinum/genetics ; Botulism ; Plasmids ; Neurons/metabolism
Chemical Substances	Neurotoxins
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.03106-23
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Botulinum Neurotoxin A4 Has a 1000-Fold Reduced Potency Due to Three Single Amino Acid Alterations in the Protein Receptor Binding Domain.

Tepp, William H / Bradshaw, Marite / Gardner, Alexander P / Kaufman, Rebecca L / Barbieri, Joseph T / Pellett, Sabine

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Botulinum neurotoxin subtype A4 (BoNT/A4) is ~1000-fold less potent than BoNT/A1. This study addresses the basis for low BoNT/A4 potency. Utilizing BoNT/A1-A4 and BoNT/A4-A1 Light Chain-Heavy Chain (LC-HC) chimeras, HC-A4 was responsible for low BoNT/A4 ... ...

Abstract	Botulinum neurotoxin subtype A4 (BoNT/A4) is ~1000-fold less potent than BoNT/A1. This study addresses the basis for low BoNT/A4 potency. Utilizing BoNT/A1-A4 and BoNT/A4-A1 Light Chain-Heavy Chain (LC-HC) chimeras, HC-A4 was responsible for low BoNT/A4 potency. Earlier studies showed BoNT/A1-receptor binding domain (Hcc) bound a β-strand peptide (556-564) and glycan-N
MeSH term(s)	Humans ; Amino Acids ; Protein Binding ; Protein Domains
Chemical Substances	Amino Acids
Language	English
Publishing date	2023-03-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065690
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Posttranslational Regulation of Botulinum Neurotoxin Production in Clostridium botulinum Hall A-

Inzalaco, Heather N'te / Tepp, William H / Fredrick, Chase / Bradshaw, Marite / Johnson, Eric A / Pellett, Sabine

mSphere

2021 Volume 6, Issue 4, Page(s) e0032821

Abstract: Botulinum neurotoxins (BoNTs) are the most toxic substances known to humankind and are the causative agents of the neuroparalytic disease botulism. Despite the overall importance of BoNTs in public health and safety, as a bioterrorism concern, and in ... ...

Abstract	Botulinum neurotoxins (BoNTs) are the most toxic substances known to humankind and are the causative agents of the neuroparalytic disease botulism. Despite the overall importance of BoNTs in public health and safety, as a bioterrorism concern, and in pharmaceutical development, little is known about the molecular mechanisms mediating BoNT stability and degradation in various environments. Previous studies using Clostridium botulinum strain ATCC 3502 revealed that high levels of arginine (20 g/liter) repressed BoNT production approximately 1,000-fold. In the present study, the mechanisms of toxin reduction in arginine-enriched cultures of C. botulinum strain Hall A-
MeSH term(s)	Animals ; Arginine/metabolism ; Arginine/pharmacology ; Botulinum Toxins, Type A/biosynthesis ; Botulinum Toxins, Type A/genetics ; Clostridium botulinum/drug effects ; Clostridium botulinum/genetics ; Clostridium botulinum/metabolism ; Culture Media/chemistry ; Female ; Gene Expression Regulation ; Hydrogen-Ion Concentration ; Mice ; Mice, Inbred ICR ; Protein Processing, Post-Translational/genetics
Chemical Substances	Culture Media ; Arginine (94ZLA3W45F) ; Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/mSphere.00328-21
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Resolution of Two Steps in Botulinum Neurotoxin Serotype A1 Light Chain Localization to the Intracellular Plasma Membrane.

Gardner, Alexander / Tepp, William H / Bradshaw, Marite / Barbieri, Joseph T / Pellett, Sabine

International journal of molecular sciences

2021 Volume 22, Issue 20

Abstract: Botulinum neurotoxin serotype A (BoNT/A) is the most potent protein toxin to humans. BoNT/A light chain (LC/A) cleavage of the membrane-bound SNAP-25 has been well-characterized, but how LC/A traffics to the plasma membrane to target SNAP-25 is unknown. ... ...

Abstract	Botulinum neurotoxin serotype A (BoNT/A) is the most potent protein toxin to humans. BoNT/A light chain (LC/A) cleavage of the membrane-bound SNAP-25 has been well-characterized, but how LC/A traffics to the plasma membrane to target SNAP-25 is unknown. Of the eight BoNT/A subtypes (A1-A8), LC/A3 has a unique short duration of action and low potency that correlate to the intracellular steady state of LC/A, where LC/A1 is associated with the plasma membrane and LC/A3 is present in the cytosol. Steady-state and live imaging of LC/A3-A1 chimeras identified a two-step process where the LC/A N terminus bound intracellular vesicles, which facilitated an internal α-helical-rich domain to mediate LC/A plasma membrane association. The propensity of LC/A variants for membrane association correlated with enhanced BoNT/A potency. Understanding the basis for light chain intracellular localization provides insight to mechanisms underlying BoNT/A potency, which can be extended to applications as a human therapy.
MeSH term(s)	Animals ; Botulinum Toxins, Type A/metabolism ; Botulinum Toxins, Type A/pharmacokinetics ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Female ; Humans ; Intracellular Membranes/drug effects ; Intracellular Membranes/metabolism ; Mice ; Mice, Inbred ICR ; Protein Binding ; Synaptosomal-Associated Protein 25/metabolism ; Tumor Cells, Cultured
Chemical Substances	SNAP25 protein, human ; Synaptosomal-Associated Protein 25 ; Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2021-10-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222011115
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Botulinum neurotoxin-encoding plasmids can be conjugatively transferred to diverse clostridial strains.

Nawrocki, Erin M / Bradshaw, Marite / Johnson, Eric A

Scientific reports

2018 Volume 8, Issue 1, Page(s) 3100

Abstract: Most Group I Clostridium botulinum strains harbor botulinum neurotoxin (bont) genes on their chromosome, while some carry these genes (including bont/a, bont/b, and bont/f) on large plasmids. Prior work in our laboratory demonstrated that Group I BoNT ... ...

Abstract	Most Group I Clostridium botulinum strains harbor botulinum neurotoxin (bont) genes on their chromosome, while some carry these genes (including bont/a, bont/b, and bont/f) on large plasmids. Prior work in our laboratory demonstrated that Group I BoNT plasmids were mobilized to C. botulinum recipient strains containing the Tn916 transposon. Here, we show that Tn916 is nonessential for plasmid transfer. Relying on an auxotrophic donor phenotype and a plasmid-borne selectable marker, we observed the transfer of pCLJ, a 270 kb plasmid harboring two bont genes, from its host strain to various clostridia. Transfer frequency was greatest to other Group I C. botulinum strains, but the plasmid was also transferred into traditionally nontoxigenic species, namely C. sporogenes and C. butyricum. Expression and toxicity of BoNT/A4 was confirmed in transconjugants by immunoblot and mouse bioassay. These data indicate that conjugation within the genus Clostridium can occur across physiological Groups of C. botulinum, supporting horizontal gene transfer via bont-bearing plasmids. The transfer of plasmids possessing bont genes to resistant Clostridium spp. such as C. sporogenes could impact biological safety for animals and humans. These plasmids may play an environmental role in initiating death in vertebrates, leading to decomposition and nutrient recycling of animal biomass.
MeSH term(s)	Animals ; Botulinum Toxins/genetics ; Botulinum Toxins/metabolism ; Chromosomes ; Clostridiales/genetics ; Clostridium/genetics ; Clostridium botulinum/genetics ; Clostridium botulinum/metabolism ; DNA Transposable Elements/genetics ; Humans ; Mice ; Phylogeny ; Plasmids/genetics
Chemical Substances	DNA Transposable Elements ; Botulinum Toxins (EC 3.4.24.69)
Language	English
Publishing date	2018-02-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-21342-9
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article: Endogenous CRISPR-Cas Systems in Group I

Wentz, Travis G / Tremblay, Benjamin J M / Bradshaw, Marite / Doxey, Andrew C / Sharma, Shashi K / Sauer, John-Demian / Pellett, Sabine

Frontiers in microbiology

2022 Volume 12, Page(s) 787726

Abstract: Most strains of proteolytic group ... ...

Abstract	Most strains of proteolytic group I
Language	English
Publishing date	2022-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587354-4
ISSN	1664-302X
ISSN	1664-302X
DOI	10.3389/fmicb.2021.787726
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Isolation and Characterization of the Novel Botulinum Neurotoxin A Subtype 6.

Moritz, Molly S / Tepp, William H / Bradshaw, Marite / Johnson, Eric A / Pellett, Sabine

mSphere

2018 Volume 3, Issue 5

Abstract: Botulinum neurotoxins (BoNTs), the most potent toxins known to humans and the causative agent of botulism, exert their effect by entering motor neurons and cleaving and inactivating SNARE proteins, which are essential for neurotransmitter release. BoNTs ... ...

Abstract	Botulinum neurotoxins (BoNTs), the most potent toxins known to humans and the causative agent of botulism, exert their effect by entering motor neurons and cleaving and inactivating SNARE proteins, which are essential for neurotransmitter release. BoNTs are proven, valuable pharmaceuticals used to treat more than 200 neuronal disorders. BoNTs comprise 7 serotypes and more than 40 isoforms (subtypes). BoNT/A1 is the only A-subtype used clinically due to its high potency and long duration of action. While other BoNT/A subtypes have been purified and described, only BoNT/A2 is being investigated as an alternative to BoNT/A1. Here we describe subtype BoNT/A6 with improved pharmacological properties compared to BoNT/A1. It was isolated from
MeSH term(s)	Animals ; Botulinum Toxins, Type A/isolation & purification ; Botulinum Toxins, Type A/toxicity ; Cells, Cultured ; Clostridium botulinum type A ; Humans ; Neurons/drug effects
Chemical Substances	Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2018-10-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/mSphere.00466-18
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Light Chain Defines the Duration of Action of Botulinum Toxin Serotype A Subtypes.

Pellett, Sabine / Bradshaw, Marite / Tepp, William H / Pier, Christina L / Whitemarsh, Regina C M / Chen, Chen / Barbieri, Joseph T / Johnson, Eric A

mBio

2018 Volume 9, Issue 2

Abstract: Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa protein toxins organized into heavy chain (HC) and light chain (LC) domains linked by a ... ...

Abstract	Botulinum neurotoxin (BoNT) is the causative agent of botulism and a widely used pharmaceutical to treat a variety of neurological diseases. BoNTs are 150-kDa protein toxins organized into heavy chain (HC) and light chain (LC) domains linked by a disulfide bond. The HC selectively binds to neurons and aids cell entry of the enzymatically active LC. There are seven immunological BoNT serotypes (A to G); each serotype includes genetic variants, termed subtypes. Only two subtypes, BoNT/A1 and BoNT/B1, are currently used as therapeutics. BoNT serotype A (BoNT/A) subtypes A2 to A8 show distinct potency, duration of action, and pathology relative to BoNT/A1. Specifically, BoNT/A3 possesses shorter duration of action and elicits distinct symptoms in mice at high toxin doses. In this report, we analyzed the roles of LC and HC of BoNT/A3 for duration of action, neuronal cell entry, and mouse pathology by using clostridium-derived recombinant hybrid BoNTs consisting of reciprocal LC and HC (BoNTA1/A3 and BoNTA3/A1). Hybrid toxins were processed in their expression host to a dichain BoNT consisting of LC and HC linked via a disulfide bond. The LC and HC defined BoNT potency in mice and BoNT toxicity for cultured neuronal cells, while the LC defined the duration of BoNT action in cell and mouse models. Protein alignment identified a previously unrecognized region within the LC subtype A3 (LC/A3) relative to the other LC serotype A (LC/A) subtypes (low primary acid homology [LPH]) that correlated to intracellular LC localization. This study shows the utility of recombinant hybrid BoNTs with new therapeutic potential, while remaining sensitive to antitoxins and therapies to native BoNT.
MeSH term(s)	Amino Acid Sequence ; Animals ; Botulinum Toxins, Type A/chemistry ; Botulinum Toxins, Type A/metabolism ; Female ; Humans ; Mice ; Mice, Inbred ICR ; Serogroup
Chemical Substances	Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2018-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00089-18
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Immunoprecipitation of native botulinum neurotoxin complexes from Clostridium botulinum subtype A strains.

Lin, Guangyun / Tepp, William H / Bradshaw, Marite / Fredrick, Chase M / Johnson, Eric A

Applied and environmental microbiology

2015 Volume 81, Issue 2, Page(s) 481–491

Abstract: Botulinum neurotoxins (BoNTs) naturally exist as components of protein complexes containing nontoxic proteins. The nontoxic proteins impart stability of BoNTs in the gastrointestinal tract and during purification and handling. The two primary neurotoxin ... ...

Abstract	Botulinum neurotoxins (BoNTs) naturally exist as components of protein complexes containing nontoxic proteins. The nontoxic proteins impart stability of BoNTs in the gastrointestinal tract and during purification and handling. The two primary neurotoxin complexes (TCs) are (i) TC1, consisting of BoNT, nontoxin-nonhemagglutinin (NTNH), and hemagglutinins (HAs), and (ii) TC2, consisting of BoNT and NTNH (and possibly OrfX proteins). In this study, BoNT/A subtypes A1, A2, A3, and A5 were examined for the compositions of their TCs in culture extracts using immunoprecipitation (IP). IP analyses showed that BoNT/A1 and BoNT/A5 form TC1s, while BoNT/A2 and BoNT/A3 form TC2s. A Clostridium botulinum host strain expressing recombinant BoNT/A4 (normally present as a TC2) from an extrachromosomal plasmid formed a TC1 with complexing proteins from the host strain, indicating that the HAs and NTNH encoded on the chromosome associated with the plasmid-encoded BoNT/A4. Strain NCTC 2916 (A1/silent B1), which carries both an ha silent bont/b cluster and an orfX bont/a1 cluster, was also examined. IP analysis revealed that NCTC 2916 formed only a TC2 containing BoNT/A1 and its associated NTNH. No association between BoNT/A1 and the nontoxic proteins from the silent bont/b cluster was detected, although the HAs were expressed as determined by Western blotting analysis. Additionally, NTNH and HAs from the silent bont/b cluster did not form a complex in NCTC 2916. The stabilities of the two types of TC differed at various pHs and with addition of KCl and NaCl. TC1 complexes were more stable than TC2 complexes. Mouse serum stabilized TC2, while TC1 was unaffected.
MeSH term(s)	Blotting, Western ; Botulinum Toxins/chemistry ; Botulinum Toxins/isolation & purification ; Clostridium botulinum/chemistry ; Hydrogen-Ion Concentration ; Immunoprecipitation ; Multiprotein Complexes/chemistry ; Multiprotein Complexes/isolation & purification ; Protein Stability ; Proteins/analysis ; Salinity
Chemical Substances	Multiprotein Complexes ; Proteins ; Botulinum Toxins (EC 3.4.24.69)
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/AEM.02817-14
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

In stock of ZB MED Cologne/Königswinter

Zs.B 201: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5.

Pellett, Sabine / Tepp, William H / Whitemarsh, Regina C M / Bradshaw, Marite / Johnson, Eric A

Toxicon : official journal of the International Society on Toxinology

2015 Volume 107, Issue Pt A, Page(s) 37–42

Abstract: To date, over 40 subtypes of botulinum neurotoxins (BoNTs) have been identified. BoNTs are classified into 7 serotypes distinguished primarily by their antigenic properties, but also characterized by their unique SNARE targets and cleavage sites, host ... ...

Abstract	To date, over 40 subtypes of botulinum neurotoxins (BoNTs) have been identified. BoNTs are classified into 7 serotypes distinguished primarily by their antigenic properties, but also characterized by their unique SNARE targets and cleavage sites, host specificity, and duration of action. Sequencing efforts in the last decade have identified several subtypes within the serotypes. Subtypes are currently defined as distinct based solely on amino acid sequence comparison, with a similarity cut-off of 2.5% difference. Ten subtypes have been identified for BoNT/A, which is the serotype associated with the most severe human botulism and also the most commonly used serotype for clinical purposes. Analyses of several of these subtypes have revealed distinct characteristics, ranging from differences in cell entry and enzyme kinetics to differences in potency in mice and cell-model specific potency. A long-term activity study in cultured primary neurons has indicated that BoNT/A1, 2, 4, and 5 have a similar duration of action, whereas BoNT/A3 has a significantly shorter duration of action. This report describes an in vivo mouse study, showing that after local injection BoNT/A2 resulted in faster onset of local paralysis than BoNT/A1, 3, 4, and 5, whereas BoNT/A3 resulted in significantly faster recovery of motor-neuron deficiency.
MeSH term(s)	Animals ; Botulinum Toxins, Type A/classification ; Botulinum Toxins, Type A/pharmacology ; Female ; Mice ; Mice, Inbred ICR ; Motor Neurons/drug effects ; Paralysis/chemically induced ; Rotarod Performance Test ; Time Factors
Chemical Substances	Botulinum Toxins, Type A (EC 3.4.24.69)
Language	English
Publishing date	2015-12-01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	204479-1
ISSN	1879-3150 ; 0041-0101
ISSN (online)	1879-3150
ISSN	0041-0101
DOI	10.1016/j.toxicon.2015.06.021
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 501: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito