BIOL243 L7

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  • Created by: Katherine
  • Created on: 05-04-17 13:07
Give some examples of virulence factors:
Flagella (motility), O and H antigens (inhibits phagocyte killing), Vi capsule antigen (inhibits complement binding),
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What are the typical virulence factors?
Offensive: Toxins, invasins, adhesins. Non specific: Extracellular enzymes, siderophores. Defensive: Capsules, IgA proteases, Superoxide dismutase.
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Are Adhesins QS controlled?
No
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What do Adgesins do?
They aid attachment
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Give examples of adhesins:
Flagella, fimbrae and pili, and stalks
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What is Lipoteichoic aicd?
An adhesin which stickout out of the cell wall and aids in attachment. It shares many pathogenic similarities with endotoxins (lipopolysaccharides).
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What are capsules? Are the QS controlled?
An adhesin, it is QS controlled. Polysaccharide layer. It lies outside the cell envelope and it deemed part of the outer envelope of a bacterial cell.
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Adherence protein are also adhesins. Give some examples:
M protein (Streptoccocus pyogenes),
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What do adherence proteins do?
Bind to specific hold cell surfaces (specific).
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Adherence proteins also serve as...
Signalling molecules.
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What do invasins do?
Act to break down host cells in the immediate vicinity of bacterial growth (short range).
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What does Hyaluronidase do?
Attacks the interstitial cememnt of connective tissue by depolymerizing hyaluronic acid.
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What does Neuraminidase?
Produced by intestinal pathogens and degrates neuraminic acid, an intracellular cememnt of the epithelial cells.
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What do collagenases do?
They break down collagen,the framework of muscles which facilitates gas gangrene in tissue.
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What does Streptokinase and Staphylokinase do?
Convert inactive plasminogen to plasmin which digests fibrin and prevents clotting of the blood allowing more rapid diffusion of the infectious bacteria. They dissolve clots
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What does coagulase do?
It ensures that the pathogen stays localised and causes a clot
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What are the two types of bacterial toxins?
Endotoxin (LPS) and Exotoxin
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What is the Endotoxin?
It is bound to the cell and released when bacteria lyse. The action is indirect: activates many host systems that cause damage
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What is the Exotoxin?
It actively secretes proteins that act of specific targets (e.g. protein synthesis)
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Where are the endotoxins present on the gram -ve cell walls?
They are the lipopolysaccharides present in the outer membrane of gram negative cell walls.
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How many components make up Endotoxin?
3 - 0 specific polysaccharide, core polysaccharide, lipid A.
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What does the poysaccharid fraction of endotoxin do?
It makes it water soluble and immunogenic.
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What does the lipid A component of endotoxin do?
It is the toxic component
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What is the LD of endotoxins?
200-400 ug per animal - pretty weak
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What do endotoxins do?
causes host cells to release proteins (endohenous pyrogens), affects the hypothalamus, activates many host systems that cause damage, leading to: fever, shock, diarrhoea, vomiting, blood coagulation, weakness and inflammation - rarely fatal.
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How do endotoxins cause problems in the pharmaceutical industry?
Drugs contaminated with endotoxins can cause complcations.
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Exotoxins can be split into how many groups? What are they?
3- Cytolytic toxins, A-B toxins and superantigens.
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What are Cytolytic toxins?
They attack the cell constituents, causing lysis
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What do AB Toxins do?
Interfere with the function of the cell.
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What do the super antigens do?
Stimulate large numbers of immune cells: damage by extensive inflammatory response.
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How do cytolytic toxins cause damage?
They insert into the cytoplasmic membrane and form a pore or they cause an enzymatic attack of phospholipids.
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How are cytolytic toxins detected?
Via the breakdown of red blood cells (haemolysins). They also attack other cells (Leukocidins).
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If you put cytolytic toxins on a blood agar plate what would you see?
Beta-hemolysis (Streptococcu pyogenes - blood cell lysis), alpha hemolysis (E.coli - iron taken out of the blood cells) or gamma hemolysis (no hemolysis)
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How to Leukocins cause damage?
Death by insertion - decrease host resistance
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How do Lecithinase cause damage?
Death by attack
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How does the AB toxin work?
2 Subunits (A+B), B binds to the cell surface receptor. A is transported to the cytoplasm where it interferes with cell functions.
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What is the purpose of B?
To deliver A to the cell
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What happens when B binds to the cell
Conformation change and pore formation in membrane. A subunit enters the cytosol - B subunit leaves recepto. A subunit interferece with cell functioning.
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What is the AB toxin of cholera?
A 5B
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What is the AB toxin of whooping cought?
A-5B
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What is the AB toxin of Diphtheria?
AB
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What is the diptheria toxin produced by?
Produced by Corynebacterium diphtheriae
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When AB diphtheria toxin gets into the cell, what happens?
It changes EF-2 to EF-2* (blocked active site). This usually fits onto the T-RNA allowing protein synthesis so synthesis cannot happen.
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What is Diphtheria's mode of action?
B binds to host membrane. A+B enter by endocytosis. Catalytic subunit A is cleaved by held to the B subunit by disulfide bonds. Endosome vesicle acidifies and the disulfide bonds are reduced. Transmembrane domain facilitates passade of A.
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What does Diphtheria subunit A do?
The catalytic A domain ADP ribosylates elongation factor 2 (EF2). This halts protein synthesis and kills the cell.
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What is Corynebacterium diptheriae?
It causes diphtheria
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What is diphtheria?
It is an upper respiratory tract infection. Sore throat, fever - then systemic. It is transmitted from person to person (5-10% = death), it is rare in developed world - immunisation
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Where is the exotoxin encoded?
In the DNA of a temperate phage. (B phage encodes for the tox gene)
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What type of cells produce the toxin?
Only lysogenic bacterial cells - it it not lytic (doesn't kill the cell)
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What is the Botulinum neurotoxin?
BoTN
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How many types of BoTN are there?
7 (A - G)
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What does the boulinum neurotoxin do?
It blocks release of B blocks the release of Acetylcholine (induces contraction of muscle fibers) by binding to the pre-synaptic membranes on the tetmini of the stimulatory motor neurons. This inhibits contraction.
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What type of beauty therapy uses botulinum neurotoxin?
Botox - when injected into muscle below a wrinkle, it reduces contraction.
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The Botox also affect which proteins?
It cleaves SNARE proteins.
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How does the cholera toxin work
It binds to the epithelium, produces cholera toxin. It binds to a receptor, goes into the cell by endocytosis and delivers the A toxin.
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Why is cholera bad?
A toxin blocks adenylate cyclase activity so you get a massive increase in cAMP. You get dehydration and loss of nutrients via diarrhoea
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What do superantigens do?
Stimulate large numbers of immune cells
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How do superantigens work?
Stimultate over production of T cells. Bind to the VB domain of the T cell receptor (TCR) outside of the normal antifen binding region. Activate 5-25% of all T cells (Normal antigens activate 0.05% of all t cells). The t cells produce cytokines.
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Why is over activation of the T cells bad?
The t cells over produce IF-y which activated macrophages. Activated macrophages over produce IL-1,IL-6 and TNF -a. It leads to severe inflammation which leads to shock and multi-organ failure.
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Where are superantigens found?
In streptococci and staphylococci. They are mostly found in contaminated food. They are very resistant to proteases. Stable at 60'C. And can survive 2.5 - 11.
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Where is there an increased risk of exposure to toxins?
Up take of a pre-formed toxin - usually in tinned food. Colonisation and in situ toxin production - it requires a high density of pathogens within the biofilms. It also requires toxin production by quorum sensing (they talk to each other)
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What are the key features of Exotoxins?
Made by Gram+ and -ve. Protein. Secreted by vible microbes. Heat liable. Highly immunogenic. Potentially lethal. Highly toxi. Toxoidable (can be modified to remove toxicity)
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What are the key features of Endotoxins?
Made by gram -ve. Lipopolysaccharides. Part of cell membrane, released on cell lysis. Heat stable. Weakly immunogenic. Lethal at high concs. Variable toxicity. No toxoidable.
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Card 2

Front

What are the typical virulence factors?

Back

Offensive: Toxins, invasins, adhesins. Non specific: Extracellular enzymes, siderophores. Defensive: Capsules, IgA proteases, Superoxide dismutase.

Card 3

Front

Are Adhesins QS controlled?

Back

Preview of the front of card 3

Card 4

Front

What do Adgesins do?

Back

Preview of the front of card 4

Card 5

Front

Give examples of adhesins:

Back

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