Botulism and Tetanus

Popoff, Michel R.; Mazuet, Christelle; Poulain, Bernard

doi:10.1007/978-3-642-30144-5_97

Cited by 11 publications

(12 citation statements)

References 411 publications

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“…The nontoxic non-HA component of C. botulinum type A is structurally related to BoNT/A and associates with BoNT/A in a pHdependent manner to form a medium-sized botulinum complex highly resistant to acidic pH and protease degradation (Gu et al, 2012;Gu and Jin, 2013). These C. botulinum strains form BoNT complexes containing OrfX proteins instead of HAs (Hill and Smith, 2013;Popoff et al, 2013). HAs, which are found in various BoNT complex types, have been evidenced to mediate the absorption of botulinum complex from the gut.…”

Section: Discussionmentioning

confidence: 99%

“…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). However, OrfX proteins have not been found to interact with intestinal cells indicating that BoNT can itself cross the intestinal barrier without the help of additional protein.…”

Section: Discussionmentioning

confidence: 99%

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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

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…BoNT type B (BoNT/B) is commonly associated with numerous cases of food borne botulism or infant botulism in humans throughout the world (Popoff, Mazuet, & Poulain, ; Sobel, ). Although all BoNT types induce a descending flaccid paralysis, differences in the clinical picture have been observed according to the BoNT type.…”

Section: Introductionmentioning

confidence: 99%

Botulinum neurotoxin type B uses a distinct entry pathway mediated by CDC42 into intestinal cells versus neuronal cells

Connan

Voillequin

Chavez

et al. 2017

Cellular Microbiology

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Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at the neuromuscular junctions. BoNT type B (BoNT/B) most often induces mild forms of botulism with predominant dysautonomic symptoms. In food borne botulism and botulism by intestinal colonisation such as infant botulism, which are the most frequent naturally acquired forms of botulism, the digestive tract is the main entry route of BoNTs into the organism. We previously showed that BoNT/B translocates through mouse intestinal barrier by an endocytosis-dependent mechanism and subsequently targets neuronal cells, mainly cholinergic neurons, in the intestinal mucosa and musculosa. Here, we investigated the entry pathway of BoNT/B using fluorescent C-terminal domain of the heavy chain (HcB), which is involved in the binding to specific receptor(s) and entry process into target cells. While the combination of gangliosides GD /GD /GT and synaptotagmin I and to a greater extent synaptotagmin II constitutes the functional HcB receptor on NG108-15 neuronal cells, HcB only uses the gangliosides GD /GD /GT to efficiently bind to m-IC intestinal cells. HcB enters both cell types by a dynamin-dependent endocytosis, which is efficiently prevented by Dynasore, a dynamin inhibitor, and reaches a common early endosomal compartment labeled by early endosome antigen (EEA1). In contrast to neuronal cells, HcB uses a Cdc42-dependent pathway to enter intestinal cells. Then, HcB is transported to late endosomes in neuronal cells, whereas it exploits a nonacidified pathway from apical to basal lateral side of m-IC cells supporting a transcytotic route in epithelial intestinal cells.

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“…Inhalational botulism is very rare. A few cases have been reported in laboratory workers preparing concentrated BoNT by continuous centrifugation and in two patients who inhaled cocaine (review in [125]). BoNT dissemination by aerosol has been considered as a possible bioterrorist attack.…”

Section: Epidemiology Of Botulism Inmentioning

confidence: 99%

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

Popoff¹

2018

Botulinum Toxin

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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.

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Botulism and Tetanus

Cited by 11 publications

References 411 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 neurotoxin type B uses a distinct entry pathway mediated by CDC42 into intestinal cells versus neuronal cells

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

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