Botulinum neurotoxins: Perspective on their existence and as polyproteins harboring viral proteases

DasGupta, Bibhuti R.

doi:10.2323/jgam.52.1

Cited by 24 publications

(23 citation statements)

References 52 publications

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“…It was proposed that BoNT may have evolved from polyproteins harboring viral proteases [DasGupta, 2006]. The present study analyzing the positions and neighboring sequences of the bont gene clusters on ATCC 3502 revealed similar chromosomal positions of the bont gene locus in Hall A (Fig.…”

Section: Discussionsupporting

confidence: 64%

Comparison of assembled Clostridium botulinum A1 genomes revealed their evolutionary relationship

Lin

2014

Genomics

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Clostridium botulinum encompasses bacteria that produce at least one of the seven serotypes of botulinum neurotoxin (BoNT/A-G). The availability of genome sequences of four closely related Type A1 or A1(B) strains, as well as the A1-specific microarray, allowed the analysis of their genomic organizations and evolutionary relationship. The four genomes share >90% core genes and >96% functional groups. Phylogenetic analysis based on COG shows closer relations of the A1(B) strain, NCTC 2916, to B1 and F1 than A1 strains. Alignment of the genomes of the three A1 strains revealed a highly similar chromosomal structure with three small gaps in the genome of ATCC 19397 and one additional gap in the genome of Hall A, suggesting ATCC 19379 as an evolutionary intermediate between Hall A and ATCC 3502. Analyses of the four gap regions indicated potential horizontal gene transfer and recombination events important for the evolution of A1 strains.

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Section: Discussionsupporting

confidence: 64%

Comparison of assembled Clostridium botulinum A1 genomes revealed their evolutionary relationship

Lin

2014

Genomics

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“…This long-lived persistence is reminiscent of the ability of some neurotropic immune-targeting viruses, such as herpes simplex virus, human immunodeficiency virus, varicella-zoster and polio to name a few, to persist in vivo inside neuronal cells for many years [39]. Interestingly, BoNTs share some features with viruses in that some proteins are synthesized as polyproteins, which are then post-translationally cleaved to their active forms, leading to the speculation that BoNTs may share some evolutionary relatedness with human viruses [40], [41].…”

Section: Discussionmentioning

confidence: 99%

Persistence of Botulinum Neurotoxin A Subtypes 1-5 in Primary Rat Spinal Cord Cells

et al. 2014

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Botulinum neurotoxins (BoNTs) are the most poisonous substances known and cause the severe disease botulism. BoNTs have also been remarkably effective as therapeutics in treating many neuronal and neuromuscular disorders. One of the hallmarks of BoNTs, particularly serotype A, is its long persistence of 2-6 months in patients at concentrations as low as fM or pM. The mechanisms for this persistence are currently unclear. In this study we determined the persistence of the BoNT/A subtypes 1 through 5 in primary rat spinal neurons. Remarkably, the duration of intracellular enzymatic activity of BoNT/A1, /A2, /A4 and /A5 was shown to be at least 10 months. Conversely, the effects of BoNT/A3 were observed for up to ∼5 months. An intermittent dosing with BoNT/E showed intracellular activity of the shorter acting BoNT/E for 2–3 weeks, followed by reoccurrence and persistence of BoNT/A-induced SNAP-25 cleavage products.

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“…DasGupta and others have proposed that such a high level of variation is suggestive that BoNT is derived from an unidentified viral polyprotein. 33 Despite the difficulties caused by BoNT diversity in the design of broad-based anti-botulism therapeutic strategies, it is intriguing to postulate that novel BoNT-based therapeutics may yet emerge with altered SNARE specificities and pharmacokinetic behaviors. Hence, much remains to be discovered about BoNT diversity and phylogeny.…”

Section: Ganglioside Recognitionmentioning

confidence: 99%

A Structural Perspective of the Sequence Variability Within Botulinum Neurotoxin Subtypes A1-A4

Arndt

Jacobson

Abola

et al. 2006

Journal of Molecular Biology

124

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Botulinum neurotoxins: Perspective on their existence and as polyproteins harboring viral proteases

Cited by 24 publications

References 52 publications

Comparison of assembled Clostridium botulinum A1 genomes revealed their evolutionary relationship

Comparison of assembled Clostridium botulinum A1 genomes revealed their evolutionary relationship

Persistence of Botulinum Neurotoxin A Subtypes 1-5 in Primary Rat Spinal Cord Cells

A Structural Perspective of the Sequence Variability Within Botulinum Neurotoxin Subtypes A1-A4

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