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Virulence Dec 2023, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and... (Review)
Review
, a polyphyletic Gram-positive taxon of bacteria, is classified purely by their ability to produce botulinum neurotoxin (BoNT). BoNT is the primary virulence factor and the causative agent of botulism. A potentially fatal disease, botulism is classically characterized by a symmetrical descending flaccid paralysis, which is left untreated can lead to respiratory failure and death. Botulism cases are classified into three main forms dependent on the nature of intoxication; foodborne, wound and infant. The BoNT, regarded as the most potent biological substance known, is a zinc metalloprotease that specifically cleaves SNARE proteins at neuromuscular junctions, preventing exocytosis of neurotransmitters, leading to muscle paralysis. The BoNT is now used to treat numerous medical conditions caused by overactive or spastic muscles and is extensively used in the cosmetic industry due to its high specificity and the exceedingly small doses needed to exert long-lasting pharmacological effects. Additionally, the ability to form endospores is critical to the pathogenicity of the bacteria. Disease transmission is often facilitated via the metabolically dormant spores that are highly resistant to environment stresses, allowing persistence in the environment in unfavourable conditions. Infant and wound botulism infections are initiated upon germination of the spores into neurotoxin producing vegetative cells, whereas foodborne botulism is attributed to ingestion of preformed BoNT. is a saprophytic bacterium, thought to have evolved its potent neurotoxin to establish a source of nutrients by killing its host.
Topics: Infant; Humans; Clostridium botulinum; Botulism; Virulence; Neurotoxins; Botulinum Toxins
PubMed: 37157163
DOI: 10.1080/21505594.2023.2205251 -
Annual Review of Biochemistry Jun 2019Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized... (Review)
Review
Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.
Topics: Animals; Botulinum Toxins; Humans; Metalloendopeptidases; Protein Conformation; Protein Engineering; Tetanus Toxin
PubMed: 30388027
DOI: 10.1146/annurev-biochem-013118-111654 -
Toxins Aug 2020Botulinum neurotoxins (BoNTs) produced by species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an... (Review)
Review
Botulinum neurotoxins (BoNTs) produced by species are the most potent identified natural toxins. Classically, the toxic neurological syndrome is characterized by an (afebrile) acute symmetric descending flaccid paralysis. The most know typical clinical syndrome of botulism refers to the foodborne form. All different forms are characterized by the same symptoms, caused by toxin-induced neuromuscular paralysis. The diagnosis of botulism is essentially clinical, as well as the decision to apply the specific antidotal treatment. The role of the laboratory is mandatory to confirm the clinical suspicion in relation to regulatory agencies, to identify the BoNTs involved and the source of intoxication. The laboratory diagnosis of foodborne botulism is based on the detection of BoNTs in clinical specimens/food samples and the isolation of BoNT from stools. Foodborne botulism intoxication is often underdiagnosed; the initial symptoms can be confused with more common clinical conditions (i.e., stroke, myasthenia gravis, Guillain-Barré syndrome-Miller-Fisher variant, Eaton-Lambert syndrome, tick paralysis and shellfish or tetrodotoxin poisoning). The treatment includes procedures for decontamination, antidote administration and, when required, support of respiratory function; few differences are related to the different way of exposure.
Topics: Animals; Botulism; Diagnosis, Differential; Female; Food Contamination; History, 18th Century; History, 19th Century; Humans; Pregnancy
PubMed: 32784744
DOI: 10.3390/toxins12080509 -
American Family Physician Oct 2021Bioterrorism is the deliberate release of viruses, bacteria, toxins, or fungi with the goal of causing panic, mass casualties, or severe economic disruption. From 1981... (Review)
Review
Bioterrorism is the deliberate release of viruses, bacteria, toxins, or fungi with the goal of causing panic, mass casualties, or severe economic disruption. From 1981 to 2018, there were 37 bioterrorist attacks worldwide. The Centers for Disease Control and Prevention (CDC) lists anthrax, botulism, plague, smallpox, tularemia, and viral hemorrhagic fevers as category A agents that are the greatest risk to national security. An emerging infectious disease (e.g., novel respiratory virus) may also be used as a biological agent. Clinicians may be the first to recognize a bioterrorism-related illness by noting an unusual presentation, location, timing, or severity of disease. Public health authorities should be notified when a biological agent is recognized or suspected. Treatment includes proper isolation and administration of antimicrobial or antitoxin agents in consultation with regional medical authorities and the CDC. Vaccinations for biological agents are not routinely administered except for smallpox, anthrax, and Ebola disease for people at high risk of exposure. The American Academy of Family Physicians, the CDC, and other organizations provide bioterrorism training and response resources for clinicians and communities. Clinicians should be aware of bioterrorism resources.
Topics: Biological Warfare Agents; Bioterrorism; Centers for Disease Control and Prevention, U.S.; Humans; United States; Vaccines
PubMed: 34652097
DOI: No ID Found -
Archives of Toxicology Jun 2022Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons,... (Review)
Review
Tetanus and botulinum neurotoxins cause the neuroparalytic syndromes of tetanus and botulism, respectively, by delivering inside different types of neurons, metalloproteases specifically cleaving the SNARE proteins that are essential for the release of neurotransmitters. Research on their mechanism of action is intensively carried out in order to devise improved therapies based on antibodies and chemical drugs. Recently, major results have been obtained with human monoclonal antibodies and with single chain antibodies that have allowed one to neutralize the metalloprotease activity of botulinum neurotoxin type A1 inside neurons. In addition, a method has been devised to induce a rapid molecular evolution of the metalloprotease domain of botulinum neurotoxin followed by selection driven to re-target the metalloprotease activity versus novel targets with respect to the SNARE proteins. At the same time, an intense and wide spectrum clinical research on novel therapeutics based on botulinum neurotoxins is carried out, which are also reviewed here.
Topics: Botulinum Toxins, Type A; Clostridium botulinum; Humans; Neurotoxins; SNARE Proteins; Tetanus
PubMed: 35333944
DOI: 10.1007/s00204-022-03271-9 -
MMWR. Recommendations and Reports :... May 2021Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress...
Botulism is a rare, neurotoxin-mediated, life-threatening disease characterized by flaccid descending paralysis that begins with cranial nerve palsies and might progress to extremity weakness and respiratory failure. Botulinum neurotoxin, which inhibits acetylcholine release at the neuromuscular junction, is produced by the anaerobic, gram-positive bacterium Clostridium botulinum and, rarely, by related species (C. baratii and C. butyricum). Exposure to the neurotoxin occurs through ingestion of toxin (foodborne botulism), bacterial colonization of a wound (wound botulism) or the intestines (infant botulism and adult intestinal colonization botulism), and high-concentration cosmetic or therapeutic injections of toxin (iatrogenic botulism). In addition, concerns have been raised about the possibility of a bioterrorism event involving toxin exposure through intentional contamination of food or drink or through aerosolization. Neurologic symptoms are similar regardless of exposure route. Treatment involves supportive care, intubation and mechanical ventilation when necessary, and administration of botulinum antitoxin. Certain neurological diseases (e.g., myasthenia gravis and Guillain-Barré syndrome) have signs and symptoms that overlap with botulism. Before the publication of these guidelines, no comprehensive clinical care guidelines existed for treating botulism. These evidence-based guidelines provide health care providers with recommended best practices for diagnosing, monitoring, and treating single cases or outbreaks of foodborne, wound, and inhalational botulism and were developed after a multiyear process involving several systematic reviews and expert input.
Topics: Botulism; Centers for Disease Control and Prevention, U.S.; Evidence-Based Medicine; Humans; United States
PubMed: 33956777
DOI: 10.15585/mmwr.rr7002a1 -
Toxins Sep 2020Toxins are the major pathogenicity factors produced by numerous bacteria involved in severe diseases in humans and animals. Certain pathogenic bacteria synthesize only...
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 and 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.
Topics: Acetylcholine Release Inhibitors; Animals; Bacterial Toxins; Botulinum Toxins; Clostridium; Humans; Insecticides; Pore Forming Cytotoxic Proteins; Staphylococcus
PubMed: 32899816
DOI: 10.3390/toxins12090570 -
Journal of Education & Teaching in... Apr 2022Emergency medicine and pediatric residents, and pediatric emergency medicine (PEM) fellows.
AUDIENCE
Emergency medicine and pediatric residents, and pediatric emergency medicine (PEM) fellows.
INTRODUCTION
Botulism is a rare but serious cause of infant hypotonia, vomiting, and respiratory failure. The differential diagnosis and management of a hypotonic infant with progressive weakness leading to respiratory failure is a rare presentation with high morbidity and mortality.1 Infants with botulism generally present with vague complaints that progressively worsen over time.2 Recognition of descending paralysis in an infant as well as signs of respiratory failure are key to preventing an adverse outcome. A key component of botulism treatment is recognizing the need to mobilize local resources to obtain BabyBIG (botulism immune globulin). This process can and should begin in the emergency department.
EDUCATIONAL OBJECTIVES
After this simulation learners should be able to: 1) develop a differential diagnosis for the hypotonic infant, 2) recognize signs and symptoms of infant botulism, 3) recognize respiratory failure and secure the airway with appropriate rapid sequence intubation (RSI) medications, 4) initiate definitive treatment of infant botulism by mobilizing resources to obtain antitoxin, 5) continue supportive management and admit the patient to the pediatric intensive care unit (PICU), 6) understand the pathophysiology and epidemiology of infant botulism, 7) develop communication and leadership skills when evaluating and managing critically ill infants.
EDUCATIONAL METHODS
This simulation case was performed using a high-fidelity Laerdal SimBaby with intubating capabilities and real-time vital sign monitoring. Additionally, this case can be performed with low fidelity manikins with supplemental scripting and visual stimuli. With minor adjustments, this case could be modified into an oral boards case.
RESEARCH METHODS
We obtained feedback from a convenience sample of random participants after the simulation case and debrief were completed. The sample of emergency medicine residents (N=21) and PEM fellow (N=1) completed 5 questions on a 5-point Likert scale.
RESULTS
The emergency medicine residents and PEM fellow had mostly favorable feedback regarding the simulation and debriefing. Most strongly agreed or agreed that this would improve their performance in an actual clinical setting.
DISCUSSION
Infant botulism is a rare condition, presenting as vague non-specific complaints that worsen over time. It is important to differentiate infant botulism from other causes of weakness, hypotonia, and respiratory failure. This case presents learners with a high acuity, rare case of infant botulism and allows them to work through a complex pediatric patient encounter in a psychologically safe space. The presence of a standardized patient to play the patient's parent is key to assess learners' nontechnical communication skills and to increase fidelity during the simulation.
TOPICS
Infant botulism, pediatric emergency medicine, respiratory failure, hypotonia, toxicology.
PubMed: 37465443
DOI: 10.21980/J8X35W -
Journal of Education & Teaching in... Jan 2021This simulation is targeted to emergency medicine residents and medical students. This case focuses on the diagnosis and management of botulism toxicity, while...
AUDIENCE
This simulation is targeted to emergency medicine residents and medical students. This case focuses on the diagnosis and management of botulism toxicity, while highlighting the logistical complications of botulism toxicity.
INTRODUCTION
Botulism is a potentially life-threatening emergency that often presents with subtle symptoms, which can progress to paralysis and respiratory failure. A descending flaccid paralysis is typical, initially affecting smaller muscles such as oculomotor, then larger facial muscles. 1,2 Early indications of respiratory compromise are important to recognize. It is important for emergency medicine physicians to be familiar with botulism and recognize the presentation quickly to safely treat the patient. Clinical findings may include: dilated pupils, diplopia, xerostomia, dysphagia, and nausea and vomiting. 3 Treatment priorities include assessment and management of the airway, close monitoring, and coordinating with local agencies to obtain botulinum antitoxin.1.
EDUCATIONAL OBJECTIVES
By the end of this simulation learners will be able to: 1) develop a differential for descending paralysis and recognize the signs and symptoms of botulism; 2) understand the importance of consulting public health authorities to obtain botulinum antitoxin in a timely fashion; 3) recognize that botulism will progress during the time period antitoxin is obtained. Early indications of respiratory compromise are expected to worsen during this time window.Secondary learning objectives include: 4) employ advanced evaluation for neurogenic respiratory failure such as physical examination, negative inspiratory force (NIF), forced vital capacity (FVC), and partial pressure of carbon dioxide (pCO2), 5) discuss and review the pathophysiology of botulism, 6) discuss the epidemiology of botulism.
EDUCATIONAL METHODS
This simulation was conducted using a high-fidelity mannequin with intubating capabilities and real-time vital sign monitoring. Following the simulation, the participants underwent a debriefing session and discussion on botulism. This case was designed as a high-fidelity simulation, but it can be adapted to a low-fidelity simulation or case discussion.
RESEARCH METHODS
Following the simulation and debriefing session, participants were provided with a survey to rate the simulation and provide feedback to instructors. Participants were asked open-ended questions about the strengths and areas of improvement of the case, and were asked to rate how they valued the learning content of the case on a 5-point scale.
RESULTS
Emergency medicine residents expressed positive feedback on the scenario. The residents appreciated the change in clinical course of the patient over time as well as the presentation of botulism. This simulation is an effective way of teaching about botulism to emergency medicine residents. We used a primary nurse asking questions to progress the case and stimulate the learners to think about certain specific aspects of the case, such as the patient's weakness or disposition. Toxicology, botulism, emergency medicine, medical simulation.
PubMed: 37465546
DOI: 10.21980/J8FD0R