Functional characterization of botulinum neurotoxin serotype H as a hybrid of known serotypes F and A (BoNT F/A)

Analytical Chemistry
Suzanne R KalbJohn R Barr

Abstract

A unique strain of Clostridium botulinum (IBCA10-7060) was recently discovered which produces two toxins: botulinum neurotoxin (BoNT) serotype B and a novel BoNT reported as serotype H. Previous molecular assessment showed that the light chain (LC) of the novel BoNT most resembled the bont of the light chain of known subtype F5, while the C-terminus of the heavy chain (HC) most resembled the binding domain of serotype A. We evaluated the functionality of both toxins produced in culture by first incorporating an immunoaffinity step using monoclonal antibodies to purify BoNT from culture supernatants and tested each immune-captured neurotoxin with full-length substrates vesicle-associated membrane protein 2 (VAMP-2), synaptosomal-associated protein 25 (SNAP-25), syntaxin, and shortened peptides representing the substrates. The BoNT/B produced by this strain behaved as a typical BoNT/B, having immunoaffinity for anti-B monoclonal antibodies and cleaving both full length VAMP-2 and a peptide based on the sequence of VAMP-2 in the expected location. As expected, there was no activity toward SNAP-25 or syntaxin. The novel BoNT demonstrated immunoaffinity for anti-A monoclonal antibodies but did not cleave SNAP-25 as expected for BoNT...Continue Reading

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Citations

Jan 10, 2016·Toxicon : Official Journal of the International Society on Toxinology·Jiubiao GuoSheng Chen
Sep 15, 2015·Toxicon : Official Journal of the International Society on Toxinology·K K HillT J Smith
Jul 2, 2015·Toxicon : Official Journal of the International Society on Toxinology·Marco PirazziniCesare Montecucco
Aug 12, 2015·Toxicon : Official Journal of the International Society on Toxinology·Anna Rita BentivoglioLucia Ricciardi
Aug 12, 2015·Toxicon : Official Journal of the International Society on Toxinology·Roger M BenoitRichard A Kammerer
Sep 13, 2015·Toxicon : Official Journal of the International Society on Toxinology·Andreas Rummel
Apr 18, 2016·Applied Biochemistry and Biotechnology·Tzuu-Wang ChangShuowei Cai
Jun 22, 2016·Science and Engineering Ethics·Angela CiriglianoTeresa Rinaldi
Jun 14, 2016·Nature Structural & Molecular Biology·Guorui YaoRongsheng Jin
Jan 23, 2016·Scientific Reports·Jiubiao GuoSheng Chen
Feb 22, 2017·Scientific Reports·Edwin J Vazquez-CintronKonstantin Ichtchenko
Apr 24, 2018·Pathogens and Disease·Michael J Mansfield, Andrew C Doxey
Apr 2, 2019·Foodborne Pathogens and Disease·Jessica L HalpinCarolina Lúquez
Aug 5, 2017·Nature Communications·Sicai ZhangPål Stenmark
Jul 14, 2018·Toxins·Alexander P Gardner, Joseph T Barbieri
Jul 20, 2019·Toxins·Robert J HobbsChristopher D Gwenin
May 12, 2018·Toxins·Domenico Azarnia Tehran, Marco Pirazzini
Dec 24, 2017·Toxicon : Official Journal of the International Society on Toxinology·Sabine PellettEric A Johnson
Jul 25, 2021·International Journal of Molecular Sciences·Juliette Duchesne de LamotteCamille Nicoleau

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