Lecture 2.2: Toxins Flashcards
What is a Toxin?
• Substances that contribute to pathogenicity
• Major Virulence factor
• Chemicals produced by pathogens that harm tissues
• Chemicals that trigger host immune responses that cause damage
• Do not produce infection
What is Toxigenicity?
It is the ability to produce a toxin
What is Toxaemia?
It is the presence of toxin in the host’s blood
What is a Toxoid?
AN inactivated toxin used in a vaccine
What are Antitoxins?
Antibodies against a specific toxin
What are the 2 Type of Toxins?
Exotoxins and Endotoxins
Exotoxins
• Extracellular: Mostly soluble proteins secreted by bacteria
• Secreted by Gram Positive and Negative Bacteria
• Highly Specific
• High Potency
• Denatured
• Local Action
• Extremely Lethal
Endotoxins
• Lipopolysaccharides (LPS) & Structural components
• Secreted by Gram Negative Bacteria
• Released by lysis
• Low specificity
• Low potency
• Not Denatured
• Act on remote sites
What are the 3 ways Exotoxins can cause harm?
• Signalling at host cell membranes (type I)
• By damaging membranes (type II)
• By entering target cells and directly altering function (type III)
What are the 3 Classes of Toxins?
• Neurotoxin
• Enterotoxin
• Superantigens
What is Toxic Shock Syndrome caused by?
It is caused by either staphylococcus or streptococcus bacteria that produce TSST-1 Toxin
What are Symptoms of Toxic Shock Syndrome? (9)
• High fever
• Low blood pressure
• Headache
• Rapid heartbeat
• Nausea and vomiting
• Muscle pain
• Malaise and confusion
• Rashes on the soles and palms
• Peeling of the skin
What is the Mode of Action of Superantigens/Type 1 Toxins?
• They can interact with a large number of different CD4+ T cells
• This results in the promiscuous activation of T cells that secrete IL-2
• Leading to a chain reaction of cytokine synthesis
• Which terminates in the production TNF-α & IL-1
(• Similar to gram negative septic shock)
What is Staphylococcal Scalded Skin Syndrome (SSSS) caused by?
• It is caused by group II coagulase-positive staphylococci
• Mainly S.aureus
What are Symptoms of Staphylococcal Scalded Skin Syndrome (SSSS)?
• Fever
• Redness
• Bullae
• Skin Exfoliation
What is Gas Gangrene caused by?
The release of toxins by Clostridium species
What are the Symptoms of Gas Gangrene?
• The site of infection becomes inflamed
• May become a bronze or blue-black colours
• Odorous fluid may seep from the wound
• The fluid may look fizzy or frothy due to the presence gas produced from
fermentation of glucose
What is the mortality rate of Gas Gangrene?
• Due to traumatic gas gangrene occurs in approximately 25% of cases
• In non-traumatic cases, mortality occurs 67-100% of the time
How does Diagnosis of Non-Traumatic Gas Gangrene occur? (3)
Analysis of Symptoms
Necrosis of the muscles and gas production may be viewed through MRI and CT scan
Fluids from the wound may be cultured to determine if both anaerobic Clostridium and other aerobic species are present
How does Diagnosis of Traumatic Gas Gangrene occur? (3)
Analysis of Symptoms
In traumatic cases, and if the infected muscle is visible, it will appear grey, green and purple in colour
In traumatic cases, and if the infected muscle is visible, it will appear grey, green and purple in colour
How do you treat Gas Gangrene?
• Draining the wound
• Removal of infected tissues to prevent the
spreading of infection
• Implementation of antibiotics
• Hyperbaric Oxygen Therapy
Characteristics of Clostridia Bacteria
• Large
• Gram Positive
• Bacilli
• Strictly Anaerobic
• Spore Forming
• Fermentative
Species of Clostridia Bacteria
• C.perfringes
• C.difficile
• C.tetani
• C.botulinum
What are 2 components of A-B Toxins?
A: Active
B: Binding
Examples of A-B Toxins
• Cholera toxin produced by Vibrio cholera (Cholera)
• A-B neurotoxin produced by Clostridium botulinum (Botulism)
• Tetanospasmin, A-B neurotoxin produced by Clostridium tetani (Tetanus)
General Mechanism of Action of A-B Toxins (4 Steps)
- Bacterium produces and releases exotoxins
- B component of exotoxin binds to host cell receptor, and exotoxin enters cell
- A component of exotoxin alters cell function by inhibiting protein synthesis
- B component is released from the cell
What is Botulism?
Botulism is poisoning that is due to Clostridium botulinum toxin
What causes Botulism?
Botulism can occur when neurotoxin is produced in vivo by C. botulinum
Or when preformed neurotoxin is acquired in an external source such as if the toxin is ingested, injected, or inhaled
What part of the body is affected in Botulism?
It affects the peripheral nerves
Symptoms of Botulism? (11)
• No Fever
• Symmetric cranial nerve palsies
• Symmetric descending muscle weakness
• Flaccid paralysis without sensory deficits
• Tachycardia
• Nausea & Vomiting
• Slurred Speech
• Problems urinating
• Dry mouth
• Abdominal distention
• Drooping eyelids
Treatment of Botulism
Treatment is with support and antitoxin
What are the 3 Types of Botulism?
• Wound botulism
• Infant botulism (the most common form)
• Adult enteric botulism (rare)
What is the Mechanism of Action of the Botulinum Toxin?
It inhibits the release of acetylcholine
What is Tetanus? What causes it?
Tetanus is acute poisoning from a neurotoxin produced by Clostridium tetani
How long is incubation period of Tetanus?
The incubation period ranges from 2 to 50 days (average, 5 to 10 days)
Symptoms of Tetanus (5)
• Opisthotonus
• Intermittent tonic spasms of voluntary muscles
• Spasm of the masseters accounts for the name lockjaw
• Fever and sweating.
• Changes in blood pressure and fast heart rate
Treatment of Tetanus
Human tetanus immune globulin and intensive support
Mode of Action of Tetanus (7)
• The toxin enters peripheral nerve endings, binds there irreversibly
• Travels retrograde along the axons and synapses
• Ultimately enters the central nervous system
• Release of inhibitory transmitters from nerve terminals is blocked
• Unopposed muscle stimulation by acetylcholine & general tonic spasticity
• Usually with superimposed intermittent tonic seizures
• Once bound, the toxin cannot be neutralised
Worldwide Mortality Rate of Tetanus
50%
Mortality Rate of Tetanus in Untreated Adults
15 to 60%
