17. Exotoxins and endotoxins Flashcards
1
Q
What are exotoxins? 1
A
- Exotoxins are protinacious compounds secreted by bacteria eg. cholera, dystentry
2
Q
What are endotoxins? 2
A
- endotoxins and LPS (Lipid A component) are not secreted.
2. They are an integral part of gram negative membranes
3
Q
What happens in the disease process after penetration of tissues? 4
A
- after penetration, bacteria multiply in the host
- they interfere with host defenses
- they damage the host via exo and endotoxins
- effects can be localised eg. cholera in the gut, or systemic and cause massive tissue damage and disease
4
Q
How was the importance of toxins discovered? 3
A
- in 1890, bacteria were grown in culture and centrifuged, and the supernatent was purified to remove the bacteria
- supernatent was injected into an animal and caused disease
- we now know that this was due to toxin secretion
5
Q
what are the properties of toxins? 6
A
- heat labile (60-80%)
- simple, soluble proteins
- extracellular
- many are coded by plasmid genes acquired from bacteriophages - all toxins originate from bacteriophages
- rapidly transported in body
6
Q
What are the types of exotoxin? 5
A
- enterotoxin eg. cholera toxin of vibrio cholerae, target GI tract
- Cytotoxins eg. haemolysin of clostridium perfringens (gangrene)
- These damage cells and destroy membranes
- Neurotoxins eg. botulinum toxin of clostridium botulinum
- these prevent neurotransmission at NMJ
7
Q
What are enterotoxins/AB toxins? 4
A
- ‘Live’/target intestinal mucosa and stimulate cells of GI tract to act in an abnormal way
- Elicit profuse fluid secretion
- There are heat labile enterotoxins eg. ETEC (enterotoxigenic E. Coli) and Shiga toxin (shigella dysenteriae)
- made from A and B subunits
8
Q
what are cytotoxins? 6
A
- attack general tissue and kill cells by enzymatic attack
- eg. membrane disrupting cytotoxins, which bind to cholesterol in membranes of host
- forms pores in membrane of rbcs and other cells
- haemoglobin is released eg. by streptolysin O (a haemolysin) of streptococcus pyogenes
- detected as beta haemolysis of blood on agar plates eg. haemolysins lyse red blood cells
- different bacteria cause different types of haemolysis
9
Q
What is the purpose of blood agar? 4
A
- On a blood agar plate, haemolysin causes zones of clearance in the blood
- The cytotoxin forms a pore to lyse rbcs
- Haemolysin has head and corkscrew structure which punctures plasma membrane
- Pores are 2nm wide and become unsustainable
10
Q
Describe the cytotoxins of clostridium perfringens. 4
A
- phospholipasse enzymes remove charged head group from lipid of phospholipids in host cell membrane
- destabilises membrane and cell dies, non discriminating
- C. perfringens (gas gangrene) produces 12 exotoxins and one is a major toxin.
- Major roxin - alpha toxin is a phospholipase (lecithinase) and casues lysis of endothelial cells, erythrocytes, leukocytes and platelets
11
Q
What is gas gangrene? 4
A
- caused after tissue damage eg. wound or frostbite, meningitis
- can be any part of the body
- bacterial spores germinate in tissue when o2 supply is lost, anaerobic organism
- there are many spores released and the bacteria cause breakdown of tissue, leading to loss of limb
12
Q
What are neurotoxins? 5
A
- interfere with normal transmission of nerve impulses
- eg. botulinum toxin produced by clostridium botulinum
- most potent poison known - 1g can kill 10^6 people
- bioterrorism threat through food
- spore forming bacterium, anaerobic
13
Q
What is botulinum toxin? 6
A
- toxin binds to a glycoprotein on neurones
- is an AB toxin. the light chain cleaves proteases that allow Ach release
- This prevents contraction and casues flaccid paralysis
- Can enter neurone and travel down spinal cord
- casues death by respiratory paralysis
- comes from canned, improperly sterilised food and honey - spores in babys gut can lead to floppy baby syndrome
14
Q
How is botulinum toxin used as a medicine? 5
A
- Botox is used as a muscle relaxant agent, and 10^6 patients treated over 11 years
- Treats over active muscles due to serious disorders of cholinergic transmission
- For example dystonia which causes twitching
- Very small amounts are injected
- Also are used cosmetically
15
Q
Describe the cholera toxin. 6
A
- From vibrio cholerae, a curbed gram negative bacterial rod with polar flagella
- Transmitted by food and water
- Causes diarrhoea and pain, about fifteen l of water lost every day
- Most deaths are due to dehydration or money and malnutrition from sequential bouts
- Must balance fluid loss with glucose sodium chloride and NaHCO3
- Bacteria attach only no penetration
16
Q
What is the mechanism of the cholera toxin? 5
A
- Bacteria grow in gut and produced toxins
- A Sub unit delivered inside and activates Adenylyl Cyclase
- This causes blockage of sodium ion movement
- There is net movement of cl- into lumen, along with bicarbonate, which leads to water loss
- Continues as long as toxin is present, which is three to four days until Antibodies are produced
17
Q
What is the AB model of toxin action? 6
A
- Enterotoxins have one molecule subunit a and 5 molecules subunit b
2, subunit a Is enzymatically active inside the cell - No binding capacity
- Subunit b attaches to specific receptor and is biologically inactive
- So b allows a inside the cell
6.b arranged around a
18
Q
Define endotoxins. 5
A
- Heat stable lipopolusaxcharide, a diode weeny major class of toxin
- Hugh levels of endotoxins cause toxic shock by bacterial sepsis, causing death
- All have same effects including fever, low blood pressure, diarrhoea, haemorrhage and miscarriage
- Disease include salmonella, shigella, gonococci and meningococci
- In outer membrane of gram negative bacteria, lipid A is the endotoxin which is part of the lps molecule
19
Q
What is the mechanism of endotoxins? 5
A
- Lipopolysaccharide embedded in outer membrane
- When body detects low levels, it activates immune system which kills the organism responsible
- If there are late amines of endotoxin, it causes overstimulation of the immune system
4, vessels become leaky and this causes a drop in blood Pressure - The organism isn’t required to kill the host, only the endotoxin
20
Q
What is the structure of lipid a? 3
A
- Two molecules of n acetylglucosamine
2, number and length of fatty acid side chains varies and determines toxicity - Longer chains mean reduced toxicity
21
Q
How does lipid a respond to antibiotics? 5
A
- Endotoxin spread by lipid A containing vesicles blebbing off into bloodstream
- This occurs even if the infection is localised
- Antibiotics break down cells as vesicles, which releases large amounts of lipid a
- This can cause toxic shock and kill the patient
- Steroids must be given to dampen the immune response
22
Q
Summaries exotoxins. 3
A
- Varied and unique to each pathogen
- Mostly give very different symptoms
- Produced by gram positive and negative bacteria
23
Q
Summarise exotoxins and lipid a. 3
A
- Very similar and have same effects on hosts
- Cause toxic shock
- Gram negative production only
