International Proficiency Test Targeting a Large Panel of Botulinum Neurotoxin Sero- and Subtypes in Different Matrices.

Detection of botulinum neurotoxins (BoNTs) involves a combination of technical challenges that call for the execution of inter-laboratory proficiency tests (PTs) to define the performance and ease of implementation of existing diagnostic methods regarding representative BoNT toxin-types spiked in clinical, food, or environmental matrices. In the framework of the EU project EuroBioTox, we organized an international proficiency test for the detection and quantification of the clinically relevant BoNT/A, B, E, and F sero- and subtypes including concentrations as low as 0.5 ng/mL.

Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution.

Bacterial protein toxins are secreted by certain bacteria and are responsible for mild to severe diseases in humans and animals. They are among the most potent molecules known, which are active at very low concentrations. Bacterial protein toxins exhibit a wide diversity based on size, structure, and mode of action.

Toxins, Pathogenicity, Anti-Toxins, a Bicentennial Contribution.

The bicentenary of Louis Pasteur's birth raises the opportunity to revisit the activity and influence of L [...

Animal Toxins: A Historical Outlook at the Institut Pasteur of Paris.

Humans have faced poisonous animals since the most ancient times. It is recognized that certain animals, like specific plants, produce toxic substances that can be lethal, but that can also have therapeutic or psychoactive effects. The use of the term "venom", which initially designated a poison, remedy, or magic drug, is now confined to animal poisons delivered by biting.

Postpartum clostridial gangrenous metritis in 12 dairy goats in France.

Clostridial infections in goats have been associated frequently with enteric diseases or gas gangrene but very rarely with the reproductive system. We describe here 12 cases of fatal postpartum gangrenous metritis in does associated with infection by several clostridial species. Clinically, these cases were characterized by rapid onset of hyperthermia followed by death after kidding.

Editorial of the Special Issue "Toxins: Mr Hyde or Dr Jekyll?".

The 27th Annual Meeting of the French Society of Toxinology (SFET, http://sfet [...

Anaerobes and Toxins, a Tradition of the Institut Pasteur.

Louis Pasteur, one of the eminent pioneers of microbiology, discovered life without oxygen and identified the first anaerobic pathogenic bacterium. Certain bacteria were found to be responsible for specific diseases. Pasteur was mainly interested in the prevention and treatment of infectious diseases with attenuated pathogens.

Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism.

The pyrin inflammasome acts as a guard of RhoA GTPases and is central to immune defenses against RhoA-manipulating pathogens. Pyrin activation proceeds in two steps. Yet, the second step is still poorly understood.

Molecular landscape of BoNT/B bound to a membrane-inserted synaptotagmin/ganglioside complex.

Botulinum neurotoxin serotype B (BoNT/B) uses two separate protein and polysialoglycolipid-binding pockets to interact with synaptotagmin 1/2 and gangliosides. However, an integrated model of BoNT/B bound to its neuronal receptors in a native membrane topology is still lacking. Using a panel of in silico and experimental approaches, we present here a new model for BoNT/B binding to neuronal membranes, in which the toxin binds to a preassembled synaptotagmin-ganglioside GT1b complex and a free ganglioside allowing a lipid-binding loop of BoNT/B to interact with the glycone part of the synaptotagmin-associated GT1b.

C910 chemical compound inhibits the traffiking of several bacterial AB toxins with cross-protection against influenza virus.

The development of anti-infectives against a large range of AB-like toxin-producing bacteria includes the identification of compounds disrupting toxin transport through both the endolysosomal and retrograde pathways. Here, we performed a high-throughput screening of compounds blocking Rac1 proteasomal degradation triggered by the Cytotoxic Necrotizing Factor-1 (CNF1) toxin, which was followed by orthogonal screens against two toxins that hijack the endolysosomal (diphtheria toxin) or retrograde (Shiga-like toxin 1) pathways to intoxicate cells. This led to the identification of the molecule C910 that induces the enlargement of EEA1-positive early endosomes associated with sorting defects of CNF1 and Shiga toxins to their trafficking pathways.

Regulatory Networks Controlling Neurotoxin Synthesis in and .

and are Gram-positive, spore-forming, and anaerobic bacteria that produce the most potent neurotoxins, botulinum toxin (BoNT) and tetanus toxin (TeNT), responsible for flaccid and spastic paralysis, respectively. The main habitat of these toxigenic bacteria is the environment (soil, sediments, cadavers, decayed plants, intestinal content of healthy carrier animals). can grow and produce BoNT in food, leading to food-borne botulism, and in some circumstances, can colonize the intestinal tract and induce infant botulism or adult intestinal toxemia botulism.

Synergistic interaction between pH and NaCl in the limits of germination and outgrowth of Clostridium sporogenes and Group I Clostridium botulinum vegetative cells and spores after heat treatment.

Group I Clostridium botulinum and Clostridium sporogenes are physiologically and genetically closely related. Both are widely distributed in the environment and can cause foodborne botulism. In this work, a physiological study was conducted with 37 isolates from spoiled canned food and five referenced strains of C.

Core-, pan- and accessory genome analyses of : insights into genetic diversity.

is a potential opportunistic pathogen recovered from faecal samples in cases of necrotizing enterocolitis (NEC), a gastrointestinal disease affecting preterm neonates. Although the species description and name validation were published in 2018, comparative genomics are lacking. In the present study, we provide the closed genome assembly of the ATCC BAA-265 (=250.

Report from the 27th (Virtual) Meeting on Toxinology, "Toxins: Mr Hyde or Dr Jekyll?", Organized by the French Society of Toxinology, 9-10 December 2021.

The French Society of Toxinology (SFET) organized its 27th annual meeting on 9-10 December 2021 as a virtual meeting (e-RT27). The central theme of this meeting was "Toxins: Mr Hyde or Dr Jekyll?", emphasizing the latest findings on plant, fungal, algal, animal and bacterial toxins during 10 lectures, 15 oral communications (shorter lectures) and 20 posters shared by ca. 80 participants.

Clostridium perfringens Beta2 toxin forms highly cation-selective channels in lipid bilayers.

Clostridium perfringens is a potent producer of a variety of toxins. Well studied from these are five toxins (alpha, Beta (CPB), epsilon, iota and CPE) that are produced by seven toxinotype strains (A-G) of C. perfringens.

Peptoniphilus nemausensis sp. nov. A new Gram-positive anaerobic coccus isolated from human clinical samples, an emendated description of the genus Peptoniphilus and an evaluation of the taxonomic status of Peptoniphilus species with not validly published names.

A Gram-positive, anaerobic coccus isolated from a human surgical site infection was previously shown to belong to an unknown species of the genus Peptoniphilus initially proposed as 'Peptoniphilus nemausus' sp. nov., based on both 16S rRNA gene sequence identity of 97.

Identification of a non-coding RNA and its putative involvement in the regulation of tetanus toxin synthesis in Clostridium tetani.

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.

Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development.

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.

Toxemia in Human Naturally Acquired Botulism.

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.