The Botulinum Neurotoxin Complex and the Role of Ancillary Proteins

Singh, Bal Ram; Chang, Tzuu-Wang; Kukreja, Roshan; Cai, Shuowei

doi:10.1007/978-1-4614-9454-6_4

Cited by 11 publications

(14 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ANTPs play an essential role in the protection of BoNT against the stomach acidic pH and digestive proteases. However, HAs are not produced by C. botulinum E, F and certain type A strains, which are also involved in human botulism by the oral route (Simpson, 2013;Singh et al, 2014). It is noteworthy that nontoxic non-HA is synthesized by all C. botulinum types and likely retains the same function in the various corresponding botulinum complexes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall

Connan

Varela-Chavez

Mazuet

et al. 2015

Cellular Microbiology

View full text Add to dashboard Cite

Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis (botulism), which in most cases enter the organism via the digestive tract and then disseminate into the blood or lymph circulation to target autonomic and motor nerve endings. The passage way of BoNTs alone or in complex forms with associated nontoxic proteins through the epithelial barrier of the digestive tract still remains unclear. Here, we show using an in vivo model of mouse ligated intestinal loop that BoNT/B alone or the BoNT/B C-terminal domain of the heavy chain (HCcB), which interacts with cell surface receptors, translocates across the intestinal barrier. The BoNT/B or HCcB translocation through the intestinal barrier occurred via an endocytosis-dependent mechanism within 10-20 min, because Dynasore, a potent endocytosis inhibitor, significantly prevented BoNT/B as well as HCcB translocation. We also show that HCcB or BoNT/B specifically targets neuronal cells and neuronal extensions in the intestinal submucosa and musculosa expressing synaptotagmin, preferentially cholinergic neurons and to a lower extent other neuronal cell types, notably serotonergic neurons. Interestingly, rare intestinal epithelial cells accumulated HCcB suggesting that distinct cell types of the intestinal epithelium, still undefined, might mediate efficient translocation of BoNT/B.

show abstract

Section: Discussionmentioning

confidence: 99%

“…***P < 0.001 (three to five quantifications in each experiment). certain type A strains, which are also involved in human botulism by the oral route (Simpson, 2013;Singh et al, 2014). These C. botulinum strains form BoNT complexes containing OrfX proteins instead of HAs (Hill and Smith, 2013;Popoff et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall

Connan

Varela-Chavez

Mazuet

et al. 2015

Cellular Microbiology

View full text Add to dashboard Cite

show abstract

“…Botulinum complexes are synthesized in in vitro cultures and in naturally contaminated food or intestinal content. The complexes are stable at acidic pH, but dissociates at alkaline pH (≥pH 7) (reviewed in [20]).…”

Section: Botulinum Complexesmentioning

confidence: 99%

“…NTNH is highly conserved. Two main classes of botulinum complexes can be distinguished based on their composition in additional proteins, the botulinum complexes containing hemagglutinins (HAs, including HA33, HA17, and HA70) (HA-BoNT complexes) and those possessing OrfX (including OrfX1, Orfx2, and OrfX3) and P47 proteins (OrfX-BoNT complexes) [17,[20][21][22][23].…”

Section: Botulinum Complexesmentioning

confidence: 99%

“…The stoichiometry can vary according to the strain, culture conditions (culture media, temperature, period of culture, etc. ), and the method of complex preparation [20]. C. botulinum A produces three types of botulinum complexes M (medium), L (large), and LL (large/large) [24,25], whereas the other C. botulinum types yield only M and L complexes.…”

Section: Botulinum Complexesmentioning

confidence: 99%

See 1 more Smart Citation

Botulinum Toxins, Diversity, Mode of Action, Epidemiology of Botulism in France

Popoff¹

2018

Botulinum Toxin

View full text Add to dashboard Cite

Botulinum toxins (BoNTs) are the most potent toxins and are responsible for botulism, which is a neurological disease in man and animals. Botulism is characterized by flaccid paralysis and inhibition of secretions. BoNTs are produced by distinct clostridial species including Clostridium botulinum that consist in four physiological and genetic groups, atypical strains of C. baratii and C. butyricum. Recently, nonclostridial bacteria have been found to synthesize BoNTs. The particularity of BoNTs is to associate with nontoxic proteins to form large-size complexes that are resistant to acidic pH and protease degradation of the digestive tract. BoNTs are divided into 10 types based on neutralization by specific antisera and into more than 40 subtypes according to their sequence variations. All BoNTs retain a common core structure and mode of action, which consists in the inhibition of neurotransmitter release, notably acetylcholine. Human botulism occurs in three main forms: foodborne botulism, botulism by intestinal colonization including infant botulism, and wound botulism. In France, type B foodborne botulism is the most prevalent form, resulting from the traditional consumption of pork products such as home-made cured ham. Albeit less frequent, human botulism is still present in France including diverse types and origins.

show abstract

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Ambrin,

Kang,

Van Do

et al. 2024

Advanced Science

Self Cite

View full text Add to dashboard Cite

Botulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi‐dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi‐dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron‐glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1β, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A‐treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A.

show abstract

The Botulinum Neurotoxin Complex and the Role of Ancillary Proteins

Cited by 11 publications

References 104 publications

Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall

Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall

Botulinum Toxins, Diversity, Mode of Action, Epidemiology of Botulism in France

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Contact Info

Product

Resources

About