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Botulinum neurotoxi...
Botulinum neurotoxin X lacks potency in mice and in human neurons
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Gregg, Brieana M. (author)
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Matsumura, Takuhiro (author)
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Wentz, Travis G. (author)
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Tepp, William H. (author)
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Bradshaw, Marite (author)
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- Stenmark, Pål, 1976- (author)
- Stockholms universitet,Institutionen för biokemi och biofysik
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Johnson, Eric A. (author)
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Fujinaga, Yukako (author)
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Pellett, Sabine (author)
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: mBio. - 2161-2129 .- 2150-7511. ; 15:3
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Botulinum neurotoxins (BoNTs) are a class of toxins produced by Clostridium botulinum (C. botulinum) and other species of Clostridia. BoNT/X is a putative novel botulinum neurotoxin identified through genome sequencing and capable of SNARE cleavage, but its neurotoxic potential in humans and vertebrates remained unclear. The C. botulinum strain producing BoNT/X, Strain 111, encodes both a plasmid-borne bont/b2 as well as the chromosomal putative bont/x. This study utilized C. botulinum Strain 111 from Japan as well as recombinantly produced full-length BoNT/X to more fully analyze this putative pathogenic toxin. We confirmed production of full-length, catalytically active native BoNT/X by C. botulinum Strain 111, produced as a disulfide-bonded dichain polypeptide similar to other BoNTs. Both the purified native and the recombinant BoNT/X had high enzymatic activity in vitro but displayed very low potency in human-induced pluripotent stem cell-derived neuronal cells and in mice. Intraperitoneal injection of up to 50 µg of native BoNT/X in mice did not result in botulism; however, mild local paralysis was observed after injection of 2 μg into the gastrocnemius muscle. We further demonstrate that the lack of toxicity by BoNT/X is due to inefficient neuronal cell association and entry, which can be rescued by replacing the receptor binding domain of BoNT/X with that of BoNT/A. These data demonstrate that BoNT/X is not a potent vertebrate neurotoxin like the classical seven serotypes of BoNTs.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- botulinum neurotoxin
- BoNT
- Clostridium botulinum
- BoNT/X
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Gregg, Brieana M ...
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Matsumura, Takuh ...
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Wentz, Travis G.
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Tepp, William H.
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Bradshaw, Marite
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Stenmark, Pål, 1 ...
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show more...
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Johnson, Eric A.
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Fujinaga, Yukako
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Pellett, Sabine
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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mBio
- By the university
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Stockholm University