Name: diphtheria toxin and its effects
Uploaded: 2026-03-12T13:35:51.000Z
Duration: 1 min 28 s
Channel: JoVE

Diphtheria, a respiratory tract infection, is caused by Corynebacterium diphtheriae, a non-spore-forming, gram-positive bacterium.It is characterized by sore throat, fever, coughing, nasal discharge, and progressive difficulty breathing in severe cases.In the environment, some strains of Corynebacterium diphtheriae are infected by a bacteriophage carrying the tox gene. The phage genome integrates into the bacterial chromosome, enabling exotoxin production.Diphtheria is transmitted through respiratory droplets or by contact with contaminated surfaces.Upon host entry, the bacteria adhere to epithelial cells in the upper respiratory tract, where they multiply and remain localized, releasing exotoxin.Diphtheria exotoxin has two subunits, A and B. Subunit B attaches to host cell receptors, triggering uptake of toxin by endocytosis.The A subunit blocks the elongation factor on ribosomes, halting protein synthesis.This causes rapid cell death, forming a thick pseudomembrane in the throat that blocks the airways.

diphtheria

Diphtheria

Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod that lacks spore-forming capability and exhibits a characteristic club-shaped morphology under microscopic examination. While C. diphtheriae can asymptomatically colonize mucosal surfaces, clinical disease manifests only when the bacterial strain is lysogenized by a specific &#946;-corynephage. This phage integrates into the bacterial genome and enables the expression of the tox gene, which encodes diphtheria toxin&#8212;the major virulence determinant responsible for local tissue destruction and systemic complications. Immunization with the diphtheria toxoid vaccine induces neutralizing antibodies against the toxin, rather than the bacterium itself, and has dramatically reduced disease incidence worldwide.Mechanism of Toxin ActionThe virulence of C. diphtheriae is primarily mediated by diphtheria toxin, which disrupts host cellular processes through the following mechanism: The toxin is a single polypeptide chain composed of two functional subunits. Fragment B facilitates attachment to the host cell membrane by binding to the heparin-binding EGF-like growth factor receptor, while fragment A serves as the active enzymatic domain. Following receptor-mediated endocytosis, acidification within the endosome induces conformational changes that allow the translocation of fragment A into the cytoplasm. Once internalized, fragment A catalyzes the ADP-ribosylation of elongation factor 2 (EF-2), a key factor in the translocation step of protein synthesis, which utilizes GTP during its function. This post-translational modification irreversibly inactivates EF-2, effectively halting protein production and ultimately triggering cell death.Pathological and Systemic EffectsThe local effects of toxin-mediated cell death in the pharyngeal epithelium include necrosis, inflammation, and the accumulation of fibrin and cellular debris, culminating in the formation of a dense, adherent pseudomembrane. This membrane typically develops within a few days of symptom onset and can obstruct the airway, particularly in pediatric patients. If the exotoxin disseminates into the bloodstream, it may target distant organs, especially the myocardium and peripheral nerves. Myocarditis, a frequent and potentially fatal complication, can emerge within the first two weeks and may present with arrhythmias, conduction abnormalities, or heart block. Neurologic involvement may include cranial nerve palsies and polyneuropathy. Early administration of diphtheria antitoxin&#8212;which neutralizes unbound circulating toxin&#8212;remains the cornerstone of treatment and is most effective when given before extensive tissue binding occurs. Antibiotics are administered concurrently to eliminate the bacterial source. Long-term prevention relies on immunization with a diphtheria toxoid vaccine, which induces robust antibody-mediated protection against the toxin and has significantly reduced the global disease burden.

Diphtheria is an acute, toxin-mediated infectious disease that primarily affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, ...

https://cloudfront.jove.com/files/ftp_upload/40828/40828_article_thumb_40828.jpg

Education

JoVE Core

Microbiology

Unit

Bacterial Diseases

KEY TERMS AND CONCEPTS

diphtheria toxin and its effects

Diphtheria is a toxin-mediated bacterial disease that usually affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod with a club-shaped form under the microscope. The bacteria can live on mucosal surfaces without causing symptoms. Clinical disease develops only when the strain is lysogenized by a specific β-corynephage that carries the tox gene for diphtheria toxin.

Diphtheria toxin is the main virulence factor, or disease-causing factor, in C. diphtheriae. It is a single polypeptide with two functional parts. Fragment B helps the toxin bind to the host cell membrane by attaching to the heparin-binding EGF-like growth factor receptor. Fragment A is the active enzyme domain. After receptor-mediated endocytosis, or cell uptake through a receptor, endosome acidification triggers a change that moves fragment A into the cytoplasm.

Once inside the cell, fragment A ADP-ribosylates elongation factor 2, also called EF-2. EF-2 is needed for the translocation step in protein synthesis, which uses GTP. This modification irreversibly inactivates EF-2. As a result, protein production stops and the cell dies.

The local damage in the pharyngeal epithelium includes necrosis, inflammation, and a buildup of fibrin and cell debris. These changes form a dense, adherent pseudomembrane within a few days of symptom onset. In children, this membrane can block the airway. If the exotoxin spreads through the bloodstream, it can affect distant organs, especially the heart muscle and peripheral nerves.

Myocarditis is a common and potentially fatal complication. It may appear within the first two weeks and can cause arrhythmias, conduction problems, or heart block. Nervous system effects can include cranial nerve palsies and polyneuropathy. Early diphtheria antitoxin is the main treatment because it neutralizes toxin that is still unbound in the blood. It works best before the toxin attaches widely to tissue. Antibiotics are given at the same time to remove the bacterial source.

Prevention depends on immunization with the diphtheria toxoid vaccine. The vaccine causes neutralizing antibodies against the toxin, not against the bacterium itself. This protection has greatly lowered disease rates around the world.

Diphtheria Toxin and Its Effects

staphylococcal skin infections

How Staph Evades the Skin Barrier

Staphylococcus aureus can live harmlessly on the skin and mucous membranes of healthy people. When the skin barrier is broken, it can switch from a commensal organism to an opportunistic pathogen. It then uses surface adhesins, or attachment proteins, such as clumping factor B and Staphylococcus aureus surface protein G (SasG) to bind damaged epidermal proteins like loricrin and cytokeratin. After attachment, S. aureus uses immune evasion tools to stay on the skin. Protein A binds the Fc...

acne infection

How Acne Forms and Changes

Acne forms when pores in sebaceous skin become blocked and inflamed. It is a common skin condition in adolescents and young adults, and it often appears on the face, neck, chest, and back. The main lesions include comedones, papules, pustules, nodules, and, in severe cases, cysts. The process starts with extra sebum production and follicular hyperkeratinization, which means the lining of the hair follicle sheds and thickens too much. These changes trap oil and keratin inside the follicle.

inhalation anthrax

Bacillus Anthracis Infection Pathways

Bacillus anthracis is a Gram-positive, spore-forming bacterium that causes anthrax. It is a zoonotic disease, which means it can spread from animals to humans. Herbivorous animals are the main hosts, but people can become infected through skin contact, eating contaminated meat, or breathing in spores. Cutaneous anthrax is the most common form. It usually starts when spores enter through small skin breaks, and it is generally less severe. Gastrointestinal anthrax comes from eating undercooked...

rocky mountain spotted fever

Tick Bite to Fever: RMSF Spread

Rocky Mountain spotted fever is a serious tick-borne disease caused by Rickettsia rickettsii, a Gram-negative bacterium with a coccobacillary shape. It lives inside host cells, so it is an obligate intracellular parasite. Infection begins when an infected tick bites the skin and passes the bacterium to a person. In the United States, the main tick vectors are Dermacentor variabilis, the American dog tick, and Dermacentor andersoni, the Rocky Mountain wood tick. Other tick species can also...

bacterial meningitis

How Bacteria Reach the Meninges

Bacterial meningitis is a severe infection that inflames the meninges, the protective membranes around the brain and spinal cord. It develops when pathogenic bacteria cross the blood-brain barrier and enter the cerebrospinal fluid (CSF), the fluid that surrounds the brain and spinal cord. Common causes include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. Pathogenic bacteria usually reach the meninges by...

tetanus

Tetanus Toxin and Muscle Spasms

Tetanus is a life-threatening neurological disorder that causes persistent muscle contractions and spastic paralysis. It is caused by Clostridium tetani, a motile, Gram-positive, rod-shaped, obligate anaerobe. The bacteria form terminal endospores, which give them a distinctive lollipop or tennis-racket appearance.

botulism

Botulism Toxin and Nerve Blockage

Botulism is a life-threatening disease caused by botulinum neurotoxin made by Clostridium botulinum, a Gram-positive, spore-forming, obligate anaerobe. Adults can develop botulism in different ways. In foodborne botulism, the body absorbs toxin that was already formed in food. In wound botulism, spores grow in injured tissue and release toxin into the blood. Infant botulism works differently from adult botulism. It often begins after an infant swallows spores, such as those found in honey, and...

plague

Plague Transmission and Symptoms

Plague is a serious zoonotic disease caused by Yersinia pestis, a Gram-negative, facultatively anaerobic coccobacillus. The bacterium mainly circulates in rodent populations. Humans usually become infected through the bite of infected fleas. It can also spread by direct contact with infected animal tissue or by inhaling respiratory droplets from a person with pneumonic plague. Y. pestis uses several virulence factors to survive in the host. In the flea, it forms biofilms in the foregut that...

streptococcal pharyngitis

Strep Throat: How It Spreads

Strep throat is an acute infection of the oropharyngeal tissues caused by Group A Streptococcus, or Streptococcus pyogenes. It spreads mainly through respiratory droplets that are released when an infected person coughs, sneezes, or talks. After the bacteria enter the body, they attach to the mucosal cells of the pharynx. Surface structures such as lipoteichoic acid and the antiphagocytic M protein help the bacteria stick to tissue. The M protein also blocks complement activation and...

Diphtheria is a toxin-mediated bacterial disease that usually affects the upper respiratory tract. It is caused by Corynebacterium diphtheriae, a Gram-positive, pleomorphic rod with a club-shaped form under the microscope. The bacteria can live on mucosal surfaces without causing symptoms. Clinical disease develops only when the strain is lysogenized by a specific β-corynephage that carries the tox gene for diphtheria toxin. Diphtheria toxin is the main virulence factor, or disease-causing...

atypical pneumonia

Walking Pneumonia: Causes and Diagnosis

Atypical pneumonia is a lung infection that often causes walking pneumonia. It is commonly caused by Mycoplasma pneumoniae, a pleomorphic bacterium with no rigid cell wall. That missing cell wall makes it resistant to beta-lactam antibiotics and shapes how it behaves in the human body. Other pathogens can also cause this disease. These include Legionella pneumophila, Coxiella burnetii, and Chlamydia psittaci. Each one is linked to different environmental or zoonotic exposures, which means the...

tuberculosis

TB Spread, Latency, and Reactivation

Tuberculosis is a lung infection caused by Mycobacterium tuberculosis, and it spreads through the air. When a person with active TB coughs or breathes out, tiny droplet nuclei can be inhaled by someone else. These particles reach the alveoli, the small air sacs in the lungs, where the bacteria are taken up by alveolar macrophages, a type of immune cell. Mycobacterium tuberculosis can survive inside these phagocytes because of its lipid-rich cell wall. After phagocytosis, infected macrophages...

peptic ulcer

H. pylori and Stomach Ulcers

H. pylori and stomach ulcers are linked through damage to the stomach and duodenal lining. A peptic ulcer is an erosive lesion in the gastric or duodenal wall. The most common cause is Helicobacter pylori infection, a Gram-negative, helical bacterium that can live in the stomach’s acidic environment. H. pylori survives acid by making urease, an enzyme that breaks urea into ammonia and carbon dioxide. The ammonia helps neutralize gastric acid around the bacterium, which supports colonization of...

bacterial gastroenteritis

How E. coli Triggers Gastroenteritis

Bacterial gastroenteritis is a gut infection that can cause diarrhea, abdominal cramps, and vomiting. It often begins after people ingest contaminated food or water. Pathogenic Escherichia coli strains are a frequent cause. Some E. coli strains make disease by producing Shiga toxin. These are called Shiga toxin–producing E. coli, or STEC. A well-known example is O157:H7. The toxin binds to a host glycolipid receptor called globotriaosylceramide, or Gb3, and enters the cell through membrane...

cholera

Cholera Spread, Symptoms, and Rehydration

Cholera is an acute gastrointestinal disease caused by the Gram-negative bacterium Vibrio cholerae. It spreads mainly through the fecal-oral route. People usually get infected by drinking contaminated water or eating contaminated food. The bacterium is motile and belongs to the Vibrionaceae family. It is linked to waterborne outbreaks in places with poor sanitation. More than 200 serogroups of Vibrio cholerae exist, but only O1 and O139 cause epidemic cholera. The O1 serogroup, especially the...

key terms and concepts

Learn how diphtheria toxin blocks protein synthesis, forms a pseudomembrane, and can damage the heart and nerves. See how vaccine and antitoxin help.

Diphtheria Toxin and Its Effects | JoVE K12

JoVE Core Microbiology provides an engaging introduction to the microbial world and its influence on health, industry, and the environment. This comprehensive collection covers key concepts such as microbial structure, metabolism, genetics, and ecology. It introduces essential laboratory techniques and microscopy methods through visually engaging animations. Corresponding scientist-in-action videos bridge classroom concepts with real-world research and applications.

microbiology

Diphtheria Toxin and Its Effects

Description

Transcript

Tags