17. Exotoxins and endotoxins

Question 1

What are exotoxins? 1

Answer 1

1. Exotoxins are protinacious compounds secreted by bacteria eg. cholera, dystentry

Question 2

What are endotoxins? 2

Answer 2

1. endotoxins and LPS (Lipid A component) are not secreted.

2. They are an integral part of gram negative membranes

Question 3

What happens in the disease process after penetration of tissues? 4

Answer 3

1. after penetration, bacteria multiply in the host
2. they interfere with host defenses
3. they damage the host via exo and endotoxins
4. effects can be localised eg. cholera in the gut, or systemic and cause massive tissue damage and disease

Question 4

How was the importance of toxins discovered? 3

Answer 4

1. in 1890, bacteria were grown in culture and centrifuged, and the supernatent was purified to remove the bacteria
2. supernatent was injected into an animal and caused disease
3. we now know that this was due to toxin secretion

Question 5

what are the properties of toxins? 6

Answer 5

1. heat labile (60-80%)
2. simple, soluble proteins
3. extracellular
4. many are coded by plasmid genes acquired from bacteriophages - all toxins originate from bacteriophages
5. rapidly transported in body

Question 6

What are the types of exotoxin? 5

Answer 6

1. enterotoxin eg. cholera toxin of vibrio cholerae, target GI tract
2. Cytotoxins eg. haemolysin of clostridium perfringens (gangrene)
3. These damage cells and destroy membranes
4. Neurotoxins eg. botulinum toxin of clostridium botulinum
5. these prevent neurotransmission at NMJ

Question 7

What are enterotoxins/AB toxins? 4

Answer 7

1. ‘Live’/target intestinal mucosa and stimulate cells of GI tract to act in an abnormal way
2. Elicit profuse fluid secretion
3. There are heat labile enterotoxins eg. ETEC (enterotoxigenic E. Coli) and Shiga toxin (shigella dysenteriae)
4. made from A and B subunits

Question 8

what are cytotoxins? 6

Answer 8

1. attack general tissue and kill cells by enzymatic attack
2. eg. membrane disrupting cytotoxins, which bind to cholesterol in membranes of host
3. forms pores in membrane of rbcs and other cells
4. haemoglobin is released eg. by streptolysin O (a haemolysin) of streptococcus pyogenes
5. detected as beta haemolysis of blood on agar plates eg. haemolysins lyse red blood cells
6. different bacteria cause different types of haemolysis

Question 9

What is the purpose of blood agar? 4

Answer 9

1. On a blood agar plate, haemolysin causes zones of clearance in the blood
2. The cytotoxin forms a pore to lyse rbcs
3. Haemolysin has head and corkscrew structure which punctures plasma membrane
4. Pores are 2nm wide and become unsustainable

Question 10

Describe the cytotoxins of clostridium perfringens. 4

Answer 10

1. phospholipasse enzymes remove charged head group from lipid of phospholipids in host cell membrane
2. destabilises membrane and cell dies, non discriminating
3. C. perfringens (gas gangrene) produces 12 exotoxins and one is a major toxin.
4. Major roxin - alpha toxin is a phospholipase (lecithinase) and casues lysis of endothelial cells, erythrocytes, leukocytes and platelets

Question 11

What is gas gangrene? 4

Answer 11

1. caused after tissue damage eg. wound or frostbite, meningitis
2. can be any part of the body
3. bacterial spores germinate in tissue when o2 supply is lost, anaerobic organism
4. there are many spores released and the bacteria cause breakdown of tissue, leading to loss of limb

Question 12

What are neurotoxins? 5

Answer 12

1. interfere with normal transmission of nerve impulses
2. eg. botulinum toxin produced by clostridium botulinum
3. most potent poison known - 1g can kill 10^6 people
4. bioterrorism threat through food
5. spore forming bacterium, anaerobic

Question 13

What is botulinum toxin? 6

Answer 13

1. toxin binds to a glycoprotein on neurones
2. is an AB toxin. the light chain cleaves proteases that allow Ach release
3. This prevents contraction and casues flaccid paralysis
4. Can enter neurone and travel down spinal cord
5. casues death by respiratory paralysis
6. comes from canned, improperly sterilised food and honey - spores in babys gut can lead to floppy baby syndrome

Question 14

How is botulinum toxin used as a medicine? 5

Answer 14

1. Botox is used as a muscle relaxant agent, and 10^6 patients treated over 11 years
2. Treats over active muscles due to serious disorders of cholinergic transmission
3. For example dystonia which causes twitching
4. Very small amounts are injected
5. Also are used cosmetically

Question 15

Describe the cholera toxin. 6

Answer 15

1. From vibrio cholerae, a curbed gram negative bacterial rod with polar flagella
2. Transmitted by food and water
3. Causes diarrhoea and pain, about fifteen l of water lost every day
4. Most deaths are due to dehydration or money and malnutrition from sequential bouts
5. Must balance fluid loss with glucose sodium chloride and NaHCO3
6. Bacteria attach only no penetration

Question 16

What is the mechanism of the cholera toxin? 5

Answer 16

1. Bacteria grow in gut and produced toxins
2. A Sub unit delivered inside and activates Adenylyl Cyclase
3. This causes blockage of sodium ion movement
4. There is net movement of cl- into lumen, along with bicarbonate, which leads to water loss
5. Continues as long as toxin is present, which is three to four days until Antibodies are produced

Question 17

What is the AB model of toxin action? 6

Answer 17

1. Enterotoxins have one molecule subunit a and 5 molecules subunit b
   2, subunit a Is enzymatically active inside the cell
2. No binding capacity
3. Subunit b attaches to specific receptor and is biologically inactive
4. So b allows a inside the cell
   6.b arranged around a

Question 18

Define endotoxins. 5

Answer 18

1. Heat stable lipopolusaxcharide, a diode weeny major class of toxin
2. Hugh levels of endotoxins cause toxic shock by bacterial sepsis, causing death
3. All have same effects including fever, low blood pressure, diarrhoea, haemorrhage and miscarriage
4. Disease include salmonella, shigella, gonococci and meningococci
5. In outer membrane of gram negative bacteria, lipid A is the endotoxin which is part of the lps molecule

Question 19

What is the mechanism of endotoxins? 5

Answer 19

1. Lipopolysaccharide embedded in outer membrane
2. When body detects low levels, it activates immune system which kills the organism responsible
3. 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
4. The organism isn’t required to kill the host, only the endotoxin

Question 20

What is the structure of lipid a? 3

Answer 20

1. Two molecules of n acetylglucosamine
   2, number and length of fatty acid side chains varies and determines toxicity
2. Longer chains mean reduced toxicity

Question 21

How does lipid a respond to antibiotics? 5

Answer 21

1. Endotoxin spread by lipid A containing vesicles blebbing off into bloodstream
2. This occurs even if the infection is localised
3. Antibiotics break down cells as vesicles, which releases large amounts of lipid a
4. This can cause toxic shock and kill the patient
5. Steroids must be given to dampen the immune response

Question 22

Summaries exotoxins. 3

Answer 22

1. Varied and unique to each pathogen
2. Mostly give very different symptoms
3. Produced by gram positive and negative bacteria

Question 23

Summarise exotoxins and lipid a. 3

Answer 23

1. Very similar and have same effects on hosts
2. Cause toxic shock
3. Gram negative production only