Bacterial toxins Flashcards
Why do bacteria use toxins?
As virulence factors to cause host damage
What are the 2 classes of toxins?
Endotoxins
Exotoxins
Describe the structure of endotoxins?
• Cell wall related toxin • Innate part of the cell called lipopolysaccharide • LPS Made up of a. O-polysaccharide b. Core polysaccharide c. Lipid A= this is the endotoxin component • Low site specificity • Integral bacterial components
Where are endotoxins released from?
From lysed or damaged cells
What are the 3 types of exotoxins?
Pore forming toxin
Enzymatic activity toxin
Super antigens
What is an example of a pore forming toxin?
Pneumolysin
What is an example of a Enzymatic activity toxin?
AB toxin
What are examples of a Super antigen?
Toxic shock syndrome toxin
Streptococcal pyrogenic exotoxins
What is the MOA of Superantigens?
Bypass t cell activation and its cascade of events
Cause massive inflammatory reaction
bind MHC II molecules
Activate large T cell number- 1 in 5
Release cytokine IL2
Bypasses complex cascade = no t cell activation and cytokine storm
What produces Toxic shock syndrome toxin and what are the signs and symptoms?
Produced by staphylococcus aureus
Involves multiple organ systems
Signs and symptoms: fever, hypotension, rash, desquamation of soles and palms
What are the types of AB toxins?
Diphtheria toxin
Botulinum toxin- BoNT
What produces diphtheria toxin?
Corynebacterium diphtheriae
Describe the microbiology of Corynebacterium diphtheriae and the effects of the Diphtheriae toxin produced?
○ Gram +Ve
○ Non-motile
○ Clubbed morphology
○ Pseudo membrane formation in throat= causes diphtheria
○ Swallowing difficulty
○ Systemic effects: heart complication, coma, death
What is the MOA of Diphtheriae toxin?
Targets protein translocation Aerosol inhaled Colonises throat Single chain AB diphtheriae toxin produced Inhibits EF2 in eukaryotic cells Inhibits protein synthesis Pseudomrmnrane formed in throat
What is the treatment option for Diphtheriae?
6 in 1 toxoid vaccine
What produces Botulinum toxin?
clostridium botulinum
Describe the microbiology of clostridium botulinum and the effects of the Botulinum toxin produced?
Enters blood stream by ingested spores which colonise GIT, wound contaminated with spores, contaminated food
Gram +ve
Motile
Rod
Obligate anaerobe
Sub terminal spores
Causes botulism= toxin mediated disease causing flaccid paralysis due to effect of toxin on peripheral nervous system
What is the MOA of Botulinum toxin?
Causes loss of excitatory pathway 1 of 3 SNARE proteins cleaved at NMJ Blocks Ach release Blocks NM transmission Mo muscle contraction Irreversible muscle relaxation and flaccid paralysis
What are the signs and symptoms of botulism?
Blurred vision Speaking difficulty Diarrhoea Vomiting Paralysis
What bacteria produce pore forming toxins?
Streptococcus pneumoniae
Group A streptococci
Escherichia coli
Staphylococcus aureus
What is the MOA of pore forming toxins?
Cytotoxic effects
Oligomerise in host membrane to form pores
○ Secreted as H2O soluble molecule
○ Recognise and bind specific target membrane receptor
○ Form multimers
○ Undergo conformational change
○ Aq pore forms in membrane
○Some toxins dissociate some remain associated with receptor
What bacteria produce Pneumolysin?
streptococcus pneumoniae
Describe the microbiology of streptococcus pneumoniae?
○ Gram +ve coccus
○ 90 capsular types
○ Non-motile
Describe the production of Pneumolysin in CAP?
It is a cytolytic cholesterol dependent toxin
Colonises lungs and causes histopathical change
Early immunosuppressive CAP= mucociliary pathway inhibited, macrophage apoptosis
Proinflammatory late CAP= neutrophil influx, complement activation, ROS production, inflammatory mediated tissue damage
Signs and symptoms of CAP: fever, malaise, dyspnoea, productive cough, purulent discharge, wheeze, chest crackle
What bacteria produces more than one type of toxin that leads to pertussis/whooping cough?
Bordetella pertussis
What toxins are produced by Bordetella pertussis and what are their MOAs?
- Pertussis toxin- enzymatic activity toxin
Immune inhibition due to reduced neutrophil recruitment - Tracheal Cytotoxin = endotoxin
Mucociliary pathway inhibition - Adenylate cyclase toxin= pore forming and enzymatic activity toxin
Immune inhibition- t cell and phagocytosis
Describe the microbiology of Bordetella pertussis?
Gram -ve
Aerobic
Cocco-bacillus
Confined to humans
What are the signs and symptoms of pertussis?
Paroxysms of cough
Secondary pneumonia
High mortality in <4 years old
Describe how the 6 in 1 toxoid vaccine works?
Exploits use of toxins by using their targets
What are the other Treatments/prevention for toxin mediated disease?
vaccine use for diphtheria and wherever possible
Antibiotic management
Anti-toxins as post exposure prophylaxis
What is the MOA of anti-toxins?
Neutralises toxin effects in the blood
