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Dr. Michel Popoff
Institut Pasteur, Paris, FRANCE

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0 Antibodies
0 Toxins
0 botulinum toxin
0 Clostridium perfringens
0 Tetanus Neurotoxin

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Clostridium
Toxins
Clostridium perfringens
Clostridium botulinum
Botulism
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Tetanus Neurotoxin
botulinum toxin

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Research article
Published: 04 April 2021 in The FASEB Journal
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Compared to conventional antisera strategies, monoclonal antibodies (mAbs) represent an alternative and safer way to treat botulism, a fatal flaccid paralysis due to botulinum neurotoxins (BoNTs). In addition, mAbs offer the advantage to be produced in a reproducible manner. We previously identified a unique and potent mouse mAb (TA12) targeting BoNT/A1 with high affinity and neutralizing activity. In this study, we characterized the molecular basis of TA12 neutralization by combining Hydrogen/Deuterium eXchange Mass Spectrometry (HDX‐MS) with site‐directed mutagenesis and functional studies. We found that TA12 recognizes a conformational epitope located at the interface between the HCN and HCC subdomains of the BoNT/A1 receptor‐binding domain (HC). The TA12‐binding interface shares common structural features with the ciA‐C2 VHH epitope and lies on the face opposite recognized by ciA‐C2‐ and the CR1/CR2‐neutralizing mAbs. The single substitution of N1006 was sufficient to affect TA12 binding to HC confirming the position of the epitope. We further uncovered that the TA12 epitope overlaps with the BoNT/A1‐binding site for both the neuronal cell surface receptor synaptic vesicle glycoprotein 2 isoform C (SV2C) and the GT1b ganglioside. Hence, TA12 potently blocks the entry of BoNT/A1 into neurons by interfering simultaneously with the binding of SV2C and to a lower extent GT1b. Our study reveals the unique neutralization mechanism of TA12 and emphasizes on the potential of using single mAbs for the treatment of botulism type A.

ACS Style

Sébastien Brier; Christine Rasetti‐Escargueil; Anne Wijkhuisen; Stéphanie Simon; Maud Marechal; Emmanuel Lemichez; Michel R. Popoff. Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A. The FASEB Journal 2021, 35, e21540 .

AMA Style

Sébastien Brier, Christine Rasetti‐Escargueil, Anne Wijkhuisen, Stéphanie Simon, Maud Marechal, Emmanuel Lemichez, Michel R. Popoff. Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A. The FASEB Journal. 2021; 35 (5):e21540.

Chicago/Turabian Style

Sébastien Brier; Christine Rasetti‐Escargueil; Anne Wijkhuisen; Stéphanie Simon; Maud Marechal; Emmanuel Lemichez; Michel R. Popoff. 2021. "Characterization of a highly neutralizing single monoclonal antibody to botulinum neurotoxin type A." The FASEB Journal 35, no. 5: e21540.

Journal article
Published: 18 February 2021 in Scientific Reports
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Clostridium tetani produces the tetanus toxin (TeNT), one of the most powerful bacterial toxins known to humankind and responsible for tetanus. The regulation of toxin expression is complex and involves the alternative sigma factor TetR as well as other regulators. Here, a transcriptional analysis of the TeNT-encoding large plasmid of C. tetani identified a putative non-coding small RNA (sRNA), located in close vicinity of the 3′ untranslated region of the tent gene. A northern blot experiment could identify a respective sRNA with a size of approx. 140 nucleotides. Sequence analysis showed that the sRNA contains a 14-nucleotide region that is complementary to a 5′ located region of tent. In order to investigate the function of the sRNA, we applied a RNA interference approach targeting the sRNA in two C. tetani wild-type strains; the constructed antisense C. tetani strains showed an approx. threefold increase in both extracellular and total TeNT production compared to the respective wild-type strains. In addition, recombinant C. tetani strains were constructed that contained tent-locus harboring plasmids with and without the sRNA. However, the introduction of the tent-locus without the sRNA in a C. tetani strain lacking the wild-type TeNT-encoding large plasmid resulted in a lower TeNT production compared to the same strain with recombinant tent-locus with the sRNA. This suggests that the expression or the effect of the sRNA is modulated by the C. tetani genetic background, notably that of the wild-type TeNT-encoding large plasmid. In addition, some recombinant strains exhibited modulated growth patterns, characterized by premature bacterial cell lysis. Taken together, our data indicate that the sRNA acts as a negative regulator of TeNT synthesis, with a possible impact on the growth of C. tetani. We hypothesize that the role of this sRNA is to limit toxin levels in the exponential growth phase in order to prevent premature bacterial lysis.

ACS Style

Holger Brüggemann; Diana Chapeton-Montes; Lucile Plourde; Michel R. Popoff. Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani. Scientific Reports 2021, 11, 1 -10.

AMA Style

Holger Brüggemann, Diana Chapeton-Montes, Lucile Plourde, Michel R. Popoff. Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani. Scientific Reports. 2021; 11 (1):1-10.

Chicago/Turabian Style

Holger Brüggemann; Diana Chapeton-Montes; Lucile Plourde; Michel R. Popoff. 2021. "Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani." Scientific Reports 11, no. 1: 1-10.

Review
Published: 22 December 2020 in Toxins
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Botulinum neurotoxins (BoNTs) show increasing therapeutic applications ranging from treatment of locally paralyzed muscles to cosmetic benefits. At first, in the 1970s, BoNT was used for the treatment of strabismus, however, nowadays, BoNT has multiple medical applications including the treatment of muscle hyperactivity such as strabismus, dystonia, movement disorders, hemifacial spasm, essential tremor, tics, cervical dystonia, cerebral palsy, as well as secretory disorders (hyperhidrosis, sialorrhea) and pain syndromes such as chronic migraine. This review summarizes current knowledge related to engineering of botulinum toxins, with particular emphasis on their potential therapeutic applications for pain management and for retargeting to non-neuronal tissues. Advances in molecular biology have resulted in generating modified BoNTs with the potential to act in a variety of disorders, however, in addition to the modifications of well characterized toxinotypes, the diversity of the wild type BoNT toxinotypes or subtypes, provides the basis for innovative BoNT-based therapeutics and research tools. This expanding BoNT superfamily forms the foundation for new toxins candidates in a wider range of therapeutic options.

ACS Style

Christine Rasetti-Escargueil; Michel R. Popoff. Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development. Toxins 2020, 13, 1 .

AMA Style

Christine Rasetti-Escargueil, Michel R. Popoff. Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development. Toxins. 2020; 13 (1):1.

Chicago/Turabian Style

Christine Rasetti-Escargueil; Michel R. Popoff. 2020. "Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development." Toxins 13, no. 1: 1.

Review
Published: 13 November 2020 in Toxins
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Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient’s sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the delay between serum sampling and disease onset. BoNT levels in patient’s sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow the differentiation between positive toxin sera from botulism and autoimmune neuropathy patients.

ACS Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. Toxemia in Human Naturally Acquired Botulism. Toxins 2020, 12, 716 .

AMA Style

Christine Rasetti-Escargueil, Emmanuel Lemichez, Michel R. Popoff. Toxemia in Human Naturally Acquired Botulism. Toxins. 2020; 12 (11):716.

Chicago/Turabian Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. 2020. "Toxemia in Human Naturally Acquired Botulism." Toxins 12, no. 11: 716.

Editorial
Published: 04 September 2020 in Toxins
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Toxins are the major pathogenicity factors produced by numerous bacteria involved in severe diseases in humans and animals. Certain pathogenic bacteria synthesize only one toxin which is responsible for all the symptoms and outcome of the disease. For example, botulinum toxins (BoNTs) and tetanus toxin (TeNT) are the unique causal factors of botulism and tetanus, respectively. Other bacteria attack the host organism by a set of multiple toxins which synergistically act to promote the disease. This is the case of Clostridium and Staphylococcus strains which secrete wide ranges of toxins such as pore-forming toxins, membrane phospholipid damaging toxins, and other cytotoxins and toxins interacting with the immune system involved in gangrene lesion generation.

ACS Style

Michel R. Popoff. Bacterial Toxins, Current Perspectives. Toxins 2020, 12, 570 .

AMA Style

Michel R. Popoff. Bacterial Toxins, Current Perspectives. Toxins. 2020; 12 (9):570.

Chicago/Turabian Style

Michel R. Popoff. 2020. "Bacterial Toxins, Current Perspectives." Toxins 12, no. 9: 570.

Journal article
Published: 22 May 2020 in Biochimica et Biophysica Acta (BBA) - Biomembranes
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Clostridium perfringens epsilon toxin (ETX) is a heptameric pore-forming toxin of the aerolysin toxin family. ETX is the most potent toxin of this toxin family and the third most potent bacterial toxin with high cytotoxic and lethal activities in animals. In addition, ETX shows a demyelinating activity in nervous tissue leading to devastating multifocal central nervous system white matter disease in ruminant animals. Pore formation in target cell membrane is most likely the initial critical step in ETX biological activity. Eight single to quadruple ETX mutants were generated by replacement of polar residues (serine, threonine, glutamine) in middle positions of the β-strands forming the β-barrel and facing the channel lumen with charged glutamic residues. Channel activity and ion selectivity were monitored in artificial lipid monolayer membranes and cytotoxicity was investigated in MDCK cells by the viability MTT test and propidium iodide entry. All the mutants formed channels with similar conductance in artificial lipid membranes and increasing cation selectivity for increasing number of mutations. Here, we show that residues in the central position of each β-strand of the amphipathic β-hairpin loop that forms the transmembrane pore, control the size and ion selectivity of the channel. While the highest cationic ETX mutants were not cytotoxic, no strict correlation was observed between ion selectivity and cytotoxicity.

ACS Style

Oliver Knapp; Elke Maier; Claudio Piselli; Roland Benz; Cezarela Hoxha; Michel R. Popoff. Central residues of the amphipathic β-hairpin loop control the properties of Clostridium perfringens epsilon-toxin channel. Biochimica et Biophysica Acta (BBA) - Biomembranes 2020, 1862, 183364 .

AMA Style

Oliver Knapp, Elke Maier, Claudio Piselli, Roland Benz, Cezarela Hoxha, Michel R. Popoff. Central residues of the amphipathic β-hairpin loop control the properties of Clostridium perfringens epsilon-toxin channel. Biochimica et Biophysica Acta (BBA) - Biomembranes. 2020; 1862 (9):183364.

Chicago/Turabian Style

Oliver Knapp; Elke Maier; Claudio Piselli; Roland Benz; Cezarela Hoxha; Michel R. Popoff. 2020. "Central residues of the amphipathic β-hairpin loop control the properties of Clostridium perfringens epsilon-toxin channel." Biochimica et Biophysica Acta (BBA) - Biomembranes 1862, no. 9: 183364.

Review
Published: 21 May 2020 in Toxins
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Botulism is a rare but severe disease which is characterized by paralysis and inhibition of secretions. Only a few cases had been reported at the end of the 19th century in France. The disease was frequent during the second world war, and then the incidence decreased progressively. However, human botulism is still present in France with 10–25 cases every year. Food-borne botulism was the main form of botulism in France, whereas infant botulism (17 cases between 2004 and 2016) was rare, and wound and inhalational botulism were exceptional. Type B was the prevalent botulism type and was mainly due to consumption of home-made or small-scale preparations of cured ham and to a lesser extent other pork meat products. In the recent period (2000–2016), a wider diversity of botulism types from various food origin including industrial foods was reported. Severe cases of type A and F botulism as well as type E botulism were more frequent. Albeit rare, the severity of botulism justifies its continued surveillance and recommendations to food industry and consumers regarding food hygiene and preservation practices.

ACS Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. Human Botulism in France, 1875–2016. Toxins 2020, 12, 338 .

AMA Style

Christine Rasetti-Escargueil, Emmanuel Lemichez, Michel R. Popoff. Human Botulism in France, 1875–2016. Toxins. 2020; 12 (5):338.

Chicago/Turabian Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. 2020. "Human Botulism in France, 1875–2016." Toxins 12, no. 5: 338.

Journal article
Published: 15 May 2020 in Toxins
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Clostridium tetani produces a potent neurotoxin, the tetanus toxin (TeNT), which is responsible for an often-fatal neurological disease (tetanus) characterized by spastic paralysis. Prevention is efficiently acquired by vaccination with the TeNT toxoid, which is obtained by C. tetani fermentation and subsequent purification and chemical inactivation. C. tetani synthesizes TeNT in a regulated manner. Indeed, the TeNT gene (tent) is mainly expressed in the late exponential and early stationary growth phases. The gene tetR (tetanus regulatory gene), located immediately upstream of tent, encodes an alternative sigma factor which was previously identified as a positive regulator of tent. In addition, the genome of C. tetani encodes more than 127 putative regulators, including 30 two-component systems (TCSs). Here, we investigated the impact of 12 regulators on TeNT synthesis which were selected based on their homology with related regulatory elements involved in toxin production in other clostridial species. Among nine TCSs tested, three of them impact TeNT production, including two positive regulators that indirectly stimulate tent and tetR transcription. One negative regulator was identified that interacts with both tent and tetR promoters. Two other TCSs showed a moderate effect: one binds to the tent promoter and weakly increases the extracellular TeNT level, and another one has a weak inverse effect. In addition, CodY (control of dciA (decoyinine induced operon) Y) but not Spo0A (sporulation stage 0) or the DNA repair protein Mfd (mutation frequency decline) positively controls TeNT synthesis by interacting with the tent promoter. Moreover, we found that inorganic phosphate and carbonate are among the environmental factors that control TeNT production. Our data show that TeNT synthesis is under the control of a complex network of regulators that are largely distinct from those involved in the control of toxin production in Clostridium botulinum or Clostridium difficile.

ACS Style

Diana Chapeton-Montes; Lucile Plourde; Cecile DeNeve; Dominique Garnier; Fabien Barbirato; Vincent Colombié; Sandy DeMay; Georges Haustant; Olivier Gorgette; Christine Schmitt; Catherine Thouvenot; Holger Brüggemann; Michel R. Popoff. Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani. Toxins 2020, 12, 328 .

AMA Style

Diana Chapeton-Montes, Lucile Plourde, Cecile DeNeve, Dominique Garnier, Fabien Barbirato, Vincent Colombié, Sandy DeMay, Georges Haustant, Olivier Gorgette, Christine Schmitt, Catherine Thouvenot, Holger Brüggemann, Michel R. Popoff. Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani. Toxins. 2020; 12 (5):328.

Chicago/Turabian Style

Diana Chapeton-Montes; Lucile Plourde; Cecile DeNeve; Dominique Garnier; Fabien Barbirato; Vincent Colombié; Sandy DeMay; Georges Haustant; Olivier Gorgette; Christine Schmitt; Catherine Thouvenot; Holger Brüggemann; Michel R. Popoff. 2020. "Tetanus Toxin Synthesis is Under the Control of A Complex Network of Regulatory Genes in Clostridium tetani." Toxins 12, no. 5: 328.

Review
Published: 30 April 2020 in Cellular Microbiology
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Numerous bacterial toxins exert their activity by inactivating or modulating a specific intracellular host target. For this purpose, these toxins have developed efficient strategies to overcome the different host cell defenses including specific binding to cell surface, internalization, passage through the endosome or plasma membrane, exploiting intracellular trafficking and addressing to intracellular targets. Several intracellularly active toxins deliver an active domain into the cytosol that interacts with a target localized to the inner face of the plasma membrane. Thus, the large clostridial glucosylating toxins (LCGTs) target Rho/Ras-GTPases, certain virulence factors of Gram negative bacteria, Rho-GTPases, while Pasteurella multocida toxin (PMT) targets trimeric G-proteins. Others such as botulinum neurotoxins and tetanus neurotoxin have their substrate on synaptic vesicle membrane. LCGTs, PMT, and certain virulence factors from Vibrio sp. show a particular structure constituted of a 4 α-helices bundle (4HBM) protruding from the catalytic site that specifically binds to the membrane phospholipids and then trap the catalytic domain at the proximity of the membrane anchored substrate. Structural and functional analysis indicate that the 4HBM tip of the Clostridium sordellii lethal toxin (TcsL) from the LCGT family contain two loops forming a cavity that mediates the binding to phospholipids and more specifically to phosphatidylserine. This article is protected by copyright. All rights reserved.

ACS Style

Carolina Varela‐Chavez; Arnaud Blondel; Michel R. Popoff. Bacterial intracellularly active toxins: Membrane localisation of the active domain. Cellular Microbiology 2020, 22, e13213 .

AMA Style

Carolina Varela‐Chavez, Arnaud Blondel, Michel R. Popoff. Bacterial intracellularly active toxins: Membrane localisation of the active domain. Cellular Microbiology. 2020; 22 (7):e13213.

Chicago/Turabian Style

Carolina Varela‐Chavez; Arnaud Blondel; Michel R. Popoff. 2020. "Bacterial intracellularly active toxins: Membrane localisation of the active domain." Cellular Microbiology 22, no. 7: e13213.

Journal article
Published: 01 April 2020 in Toxicon
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Botulinum neurotoxins (BoNTs) are highly potent toxins responsible for a severe disease, called botulism. They are also efficient therapeutic tools with an increasing number of indications ranging from neuromuscular dysfunction to hypersecretion syndrome, pain release, depression as well as cosmetic application. BoNTs are known to mainly target the motor-neurons terminals and to induce flaccid paralysis. BoNTs recognize a specific double receptor on neuronal cells consisting of gangliosides and synaptic vesicle protein, SV2 or synaptotagmin. Using cultured neuronal cells, BoNTs have been established blocking the release of a wide variety of neurotransmitters. However, BoNTs are more potent in motor-neurons than in the other neuronal cell types. In in vivo models, BoNT/A impairs the cholinergic neuronal transmission at the motor-neurons but also at neurons controlling secretions and smooth muscle neurons, and blocks several neuronal pathways including excitatory, inhibitory, and sensitive neurons. However, only a few reports investigated the neuronal selectivity of BoNTs in vivo. In the intestinal wall, BoNT/A and BoNT/B target mainly the cholinergic neurons and to a lower extent the other non-cholinergic neurons including serotonergic, glutamatergic, GABAergic, and VIP-neurons. The in vivo effects induced by BoNTs on the non-cholinergic neurons remain to be precisely investigated. We report here a literature review of the neuronal selectivity of BoNTs.

ACS Style

Bernard Poulain; Emmanuel Lemichez; Michel R. Popoff. Neuronal selectivity of botulinum neurotoxins. Toxicon 2020, 178, 20 -32.

AMA Style

Bernard Poulain, Emmanuel Lemichez, Michel R. Popoff. Neuronal selectivity of botulinum neurotoxins. Toxicon. 2020; 178 ():20-32.

Chicago/Turabian Style

Bernard Poulain; Emmanuel Lemichez; Michel R. Popoff. 2020. "Neuronal selectivity of botulinum neurotoxins." Toxicon 178, no. : 20-32.

Review
Published: 17 March 2020 in Cellular Microbiology
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Intimate interactions between the armament of pathogens and their host dictate tissue and host susceptibility to infection also forging specific pathophysiological outcomes. Studying these interactions at the molecular level has provided an invaluable source of knowledge on cellular processes, as ambitioned by the Cellular Microbiology discipline when it emerged in early 90s. Bacterial toxins act on key cell regulators or membranes to produce major diseases and therefore constitute a remarkable toolbox for dissecting basic biological processes. Here, we review selected examples of recent studies on bacterial toxins illustrating how fruitful the discipline of cellular microbiology is in shaping our understanding of eukaryote processes. This ever‐renewing discipline unveils new virulence factor biochemical activities shared by eukaryotic enzymes and hidden rules of cell proteome homeostasis, a particularly promising field to interrogate the impact of proteostasis breaching in late onset human diseases. It is integrating new concepts from the physics of soft matter to capture biomechanical determinants forging cells and tissues architecture. The success of this discipline is also grounded by the development of therapeutic tools and new strategies to treat both infectious and noncommunicable human diseases.

ACS Style

Emmanuel Lemichez; Michel Robert Popoff; Karla J. F. Satchell. Cellular microbiology: Bacterial toxin interference drives understanding of eukaryotic cell function. Cellular Microbiology 2020, 22, e13178 .

AMA Style

Emmanuel Lemichez, Michel Robert Popoff, Karla J. F. Satchell. Cellular microbiology: Bacterial toxin interference drives understanding of eukaryotic cell function. Cellular Microbiology. 2020; 22 (4):e13178.

Chicago/Turabian Style

Emmanuel Lemichez; Michel Robert Popoff; Karla J. F. Satchell. 2020. "Cellular microbiology: Bacterial toxin interference drives understanding of eukaryotic cell function." Cellular Microbiology 22, no. 4: e13178.

Review article
Published: 20 February 2020 in Bulletin de l'Académie Nationale de Médecine
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Les toxines botuliques sont des complexes de protéines formés d’une protéine neuro-active, la neurotoxine botulique (BoNT), et de protéines associées non toxiques. Toutes les indications médicales des toxines botuliques sont basées sur l’action inhibitrice de très longue durée de la BoNT sur la libération de neurotransmetteur. La BoNT est une protéine de 150 kDa qui se lie aux terminaisons nerveuses, est internalisée dans celles-ci et bloque la machinerie d’exocytose des neurotransmetteurs. Selon son sérotype la BoNT clive d’une des trois protéines SNARE impliquées dans la fusion des vésicules synaptiques avec la membrane plasmique des terminaisons nerveuses, indistinctement du type de transmetteur qu’elles contiennent. La très forte sélectivité d’action de la BoNT pour les terminaisons des neurones est principalement due à sa liaison à des récepteurs (synaptotagmine ou SV2 selon le sérotype de BoNT) qui sont des protéines des vésicules synaptiques exposées en surface des terminaisons des neurones à l’occasion de l’exocytose des neurotransmetteurs. La BoNT ne peut pas franchir la barrière hémato encéphalique. Ses effets sont majoritairement périphériques. Néanmoins, après une injection de BoNT en périphérie, une petite fraction de la neurotoxine capturée par les terminaisons nerveuses périphériques peut être transportée jusqu’aux corps cellulaires des neurones moteurs et sensitifs. La spécificité neuronale des BoNT en fait un outil thérapeutique utilisé dans de très nombreuses indications relevant de la médecine physique et de réadaptation, la neurologie, l'ophtalmologie, l'urologie et la prise en charge de la douleur. Botulinum toxins are protein complexes comprised of a neuroactive protein, botulinum neurotoxin (BoNT), and several non-toxic associated proteins. All medical indications for botulinum toxins are based on the very long-term inhibitory action of BoNT on the release of neurotransmitter. BoNT is a 150 kDa protein that binds to nerve endings, is internalized in them and blocks the vesicular neurotransmitter exocytosis machinery. Depending on its serotype, BoNT cleaves one among the three SNARE proteins involved in the fusion of synaptic vesicles with the plasma membrane of nerve endings, regardless of the type of transmitter they contain. The very high selectivity of action of BoNT for neuron nerve terminals is mainly due to its binding a protein receptor (synaptotagmin or SV2, depending on the BoNT serotype), which is a synaptic vesicle membrane protein exposed on the surface of neuron terminations during neurotransmitter exocytosis. BoNT cannot cross the blood-brain barrier, therefore, its effects are mainly peripheral. Nevertheless, after an injection of BoNT in the periphery, the neurotoxin captured by the peripheral nerve endings can be retrogradely transported inside sensory neurons where it can act, thereby modifying sensory information ascending to the central nervous system. The neuronal specificity of BoNT makes it a therapeutic tool used in a wide range of indications in physical and rehabilitation medicine, neurology, ophthalmology, urology and pain management.

ACS Style

Bernard Poulain; Michel R. Popoff. Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux. Bulletin de l'Académie Nationale de Médecine 2020, 204, 369 -378.

AMA Style

Bernard Poulain, Michel R. Popoff. Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux. Bulletin de l'Académie Nationale de Médecine. 2020; 204 (4):369-378.

Chicago/Turabian Style

Bernard Poulain; Michel R. Popoff. 2020. "Neurotoxine botulique : mécanismes moléculaires et cellulaires de son action sur le système nerveux." Bulletin de l'Académie Nationale de Médecine 204, no. 4: 369-378.

Review
Published: 18 February 2020 in Journal of Veterinary Diagnostic Investigation
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Tetanus is a neurologic disease of humans and animals characterized by spastic paralysis. Tetanus is caused by tetanus toxin (TeNT) produced by Clostridium tetani, an environmental soilborne, gram-positive, sporulating bacterium. The disease most often results from wound contamination by soil containing C. tetani spores. Horses, sheep, and humans are highly sensitive to TeNT, whereas cattle, dogs, and cats are more resistant. The diagnosis of tetanus is mainly based on the characteristic clinical signs. Identification of C. tetani at the wound site is often difficult.

ACS Style

Michel R. Popoff. Tetanus in animals. Journal of Veterinary Diagnostic Investigation 2020, 32, 184 -191.

AMA Style

Michel R. Popoff. Tetanus in animals. Journal of Veterinary Diagnostic Investigation. 2020; 32 (2):184-191.

Chicago/Turabian Style

Michel R. Popoff. 2020. "Tetanus in animals." Journal of Veterinary Diagnostic Investigation 32, no. 2: 184-191.

Journal article
Published: 06 January 2020 in Toxins
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Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intracellular pathways that block the large conductance Kir channel activity in oligodendrocyte. Altogether, these findings and previous observations pinpoint oligodendrocytes as a major target for ETX. This supports the proposal that ETX might be a cause for Multiple Sclerosis, a disease characterized by myelin damage.

ACS Style

Jean Louis Bossu; Laetitia Wioland; Frédéric Doussau; Philippe Isope; Michel R. Popoff; Bernard Poulain. Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes. Toxins 2020, 12, 36 .

AMA Style

Jean Louis Bossu, Laetitia Wioland, Frédéric Doussau, Philippe Isope, Michel R. Popoff, Bernard Poulain. Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes. Toxins. 2020; 12 (1):36.

Chicago/Turabian Style

Jean Louis Bossu; Laetitia Wioland; Frédéric Doussau; Philippe Isope; Michel R. Popoff; Bernard Poulain. 2020. "Epsilon Toxin from Clostridium perfringens Causes Inhibition of Potassium inward Rectifier (Kir) Channels in Oligodendrocytes." Toxins 12, no. 1: 36.

Meeting report
Published: 03 January 2020 in Toxins
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This 26th edition of the annual Meeting on Toxinology (RT26) of the SFET (http://sfet.asso.fr/international) was held at the Institut Pasteur of Paris on 4–5 December 2019

ACS Style

Pascale Marchot; Sylvie Diochot; Michel R. Popoff; Evelyne Benoit. Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019. Toxins 2020, 12, 31 .

AMA Style

Pascale Marchot, Sylvie Diochot, Michel R. Popoff, Evelyne Benoit. Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019. Toxins. 2020; 12 (1):31.

Chicago/Turabian Style

Pascale Marchot; Sylvie Diochot; Michel R. Popoff; Evelyne Benoit. 2020. "Report from the 26th Meeting on Toxinology, “Bioengineering of Toxins”, Organized by the French Society of Toxinology (SFET) and Held in Paris, France, 4–5 December 2019." Toxins 12, no. 1: 31.

Review
Published: 30 December 2019 in Toxins
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Botulism is a rare but severe neurological disease in man and animals that is caused by botulinum neurotoxins (BoNTs) produced by Clostridium botulinum and atypical strains from other Clostridium and non-Clostridium species. BoNTs are divided into more than seven toxinotypes based on neutralization with specific corresponding antisera, and each toxinotype is subdivided into subtypes according to amino acid sequence variations. Animal species show variable sensitivity to the different BoNT toxinotypes. Thereby, naturally acquired animal botulism is mainly due to BoNT/C, D and the mosaic variants CD and DC, BoNT/CD being more prevalent in birds and BoNT/DC in cattle, whereas human botulism is more frequently in the types A, B and E, and to a lower extent, F. Botulism is not a contagious disease, since there is no direct transmission from diseased animals or man to a healthy subject. Botulism occurs via the environment, notably from food contaminated with C. botulinum spores and preserved in conditions favorable for C. botulinum growth and toxin production. The high prevalence of botulism types C, D and variants DC and CD in farmed and wild birds, and to a lower extent in cattle, raises the risk of transmission to human beings. However, human botulism is much rarer than animal botulism, and botulism types C and D are exceptional in humans. Only 15 cases or suspected cases of botulism type C and one outbreak of botulism type D have been reported in humans to date. In contrast, animal healthy carriers of C. botulinum group II, such as C. botulinum type E in fish of the northern hemisphere, and C. botulinum B4 in pigs, represent a more prevalent risk of botulism transmission to human subjects. Less common botulism types in animals but at risk of transmission to humans, can sporadically be observed, such as botulism type E in farmed chickens in France (1998–2002), botulism type B in cattle in The Netherlands (1977–1979), botulism types A and B in horses, or botulism type A in dairy cows (Egypt, 1976). In most cases, human and animal botulisms have distinct origins, and cross transmissions between animals and human beings are rather rare, accidental events. But, due to the severity of this disease, human and animal botulism requires a careful surveillance.

ACS Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. Public Health Risk Associated with Botulism as Foodborne Zoonoses. Toxins 2019, 12, 17 .

AMA Style

Christine Rasetti-Escargueil, Emmanuel Lemichez, Michel R. Popoff. Public Health Risk Associated with Botulism as Foodborne Zoonoses. Toxins. 2019; 12 (1):17.

Chicago/Turabian Style

Christine Rasetti-Escargueil; Emmanuel Lemichez; Michel R. Popoff. 2019. "Public Health Risk Associated with Botulism as Foodborne Zoonoses." Toxins 12, no. 1: 17.

Author correction
Published: 19 November 2019 in Scientific Reports
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.

ACS Style

Diana Chapeton-Montes; Lucile Plourde; Christiane Bouchier; Laurence Ma; Laure Diancourt; Alexis Criscuolo; Michel Robert Popoff; Holger Brüggemann. Author Correction: The population structure of Clostridium tetani deduced from its pan-genome. Scientific Reports 2019, 9, 1 -1.

AMA Style

Diana Chapeton-Montes, Lucile Plourde, Christiane Bouchier, Laurence Ma, Laure Diancourt, Alexis Criscuolo, Michel Robert Popoff, Holger Brüggemann. Author Correction: The population structure of Clostridium tetani deduced from its pan-genome. Scientific Reports. 2019; 9 (1):1-1.

Chicago/Turabian Style

Diana Chapeton-Montes; Lucile Plourde; Christiane Bouchier; Laurence Ma; Laure Diancourt; Alexis Criscuolo; Michel Robert Popoff; Holger Brüggemann. 2019. "Author Correction: The population structure of Clostridium tetani deduced from its pan-genome." Scientific Reports 9, no. 1: 1-1.

Review
Published: 12 September 2019 in Toxins
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Botulinum neurotoxin (BoNT) is produced by the anaerobic, Gram-positive bacterium Clostridium botulinum. As one of the most poisonous toxins known and a potential bioterrosism agent, BoNT is characterized by a complex mode of action comprising: internalization, translocation and proteolytic cleavage of a substrate, which inhibits synaptic exocytotic transmitter release at neuro-muscular nerve endings leading to peripheral neuroparalysis of the skeletal and autonomic nervous systems. There are seven major serologically distinct toxinotypes (A–G) of BoNT which act on different substrates. Human botulism is generally caused by BoNT/A, B and E. Due to its extreme lethality and potential use as biological weapon, botulism remains a global public health concern. Vaccination against BoNT, although an effective strategy, remains undesirable due to the growing expectation around therapeutic use of BoNTs in various pathological conditions. This review focuses on the current approaches for botulism control by immunotherapy, highlighting the future challenges while the molecular underpinnings among subtypes variants and BoNT sequences found in non-clostridial species remain to be elucidated.

ACS Style

Christine Rasetti-Escargueil; Michel R. Popoff; Rasetti- Escargueil. Antibodies and Vaccines Against Botulinum Toxins: Available Measures and Novel Approaches. Toxins 2019, 11, 528 .

AMA Style

Christine Rasetti-Escargueil, Michel R. Popoff, Rasetti- Escargueil. Antibodies and Vaccines Against Botulinum Toxins: Available Measures and Novel Approaches. Toxins. 2019; 11 (9):528.

Chicago/Turabian Style

Christine Rasetti-Escargueil; Michel R. Popoff; Rasetti- Escargueil. 2019. "Antibodies and Vaccines Against Botulinum Toxins: Available Measures and Novel Approaches." Toxins 11, no. 9: 528.

Journal article
Published: 02 August 2019 in Scientific Reports
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Clostridium tetani produces a potent neurotoxin, the tetanus neurotoxin (TeNT) that is responsible for the worldwide neurological disease tetanus, but which can be efficiently prevented by vaccination with tetanus toxoid. Until now only one type of TeNT has been characterized and very little information exists about the heterogeneity among C. tetani strains. We report here the genome sequences of 26 C. tetani strains, isolated between 1949 and 2017 and obtained from different locations. Genome analyses revealed that the C. tetani population is distributed in two phylogenetic clades, a major and a minor one, with no evidence for clade separation based on geographical origin or time of isolation. The chromosome of C. tetani is highly conserved; in contrast, the TeNT-encoding plasmid shows substantial heterogeneity. TeNT itself is highly conserved among all strains; the most relevant difference is an insertion of four amino acids in the C-terminal receptor-binding domain in four strains that might impact on receptor-binding properties. Other putative virulence factors, including tetanolysin and collagenase, are encoded in all genomes. This study highlights the population structure of C. tetani and suggests that tetanus-causing strains did not undergo extensive evolutionary diversification, as judged from the high conservation of its main virulence factors.

ACS Style

Diana Chapeton-Montes; Lucile Plourde; Christiane Bouchier; Laurence Ma; Laure Diancourt; Alexis Criscuolo; Michel Robert Popoff; Holger Brüggemann. The population structure of Clostridium tetani deduced from its pan-genome. Scientific Reports 2019, 9, 1 -11.

AMA Style

Diana Chapeton-Montes, Lucile Plourde, Christiane Bouchier, Laurence Ma, Laure Diancourt, Alexis Criscuolo, Michel Robert Popoff, Holger Brüggemann. The population structure of Clostridium tetani deduced from its pan-genome. Scientific Reports. 2019; 9 (1):1-11.

Chicago/Turabian Style

Diana Chapeton-Montes; Lucile Plourde; Christiane Bouchier; Laurence Ma; Laure Diancourt; Alexis Criscuolo; Michel Robert Popoff; Holger Brüggemann. 2019. "The population structure of Clostridium tetani deduced from its pan-genome." Scientific Reports 9, no. 1: 1-11.

Journal article
Published: 01 March 2019 in Toxins
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Clostridiumperfringens type E is a less frequently isolated C.perfringens type and has not previously been reported in France. We have characterized two recent type E isolates, C.perfringens 508.17 from the intestinal content of a calf that died of enterotoxemia, and 515.17 from the stool of a 60-year-old woman, subsequent to food poisoning, which contained the plasmid pCPPB-1 with variant iota toxin and C. perfringens enterotoxin genes.

ACS Style

Laure Diancourt; Jean Sautereau; Alexis Criscuolo; Michel R. Popoff. Two Clostridiumperfringens Type E Isolates in France. Toxins 2019, 11, 138 .

AMA Style

Laure Diancourt, Jean Sautereau, Alexis Criscuolo, Michel R. Popoff. Two Clostridiumperfringens Type E Isolates in France. Toxins. 2019; 11 (3):138.

Chicago/Turabian Style

Laure Diancourt; Jean Sautereau; Alexis Criscuolo; Michel R. Popoff. 2019. "Two Clostridiumperfringens Type E Isolates in France." Toxins 11, no. 3: 138.