Bacterial Pathogens And Disease 1 - Exotoxins Flashcards

1
Q

What do antibodies do?

A

Opsonise
Activate complement
Neutralise

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2
Q

What is a pathogen?

A

Microorganism capable of causing disease

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3
Q

What is pathogenicity?

A

The ability of an infectious agent to cause disease

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4
Q

What is virulence?

A

Quantitative ability of an agent to cause disease

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5
Q

What is toxigenicity?

A

The ability of a microorganism to produce a toxin that contributes to the development of a disease

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6
Q

What are the mechanisms of virulence?

A

Adherence
Biofilms
Invasion of host cells and tissues
Toxins

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7
Q

What are endotoxins?

A

Heterogeneous group of proteins produced and secreted by lining bacterial cells

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8
Q

What type of bacteria are endotoxins produced by?

A

Both gram positive and negative bacteria

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9
Q

What do endotoxins do?

A

Cause disease symptoms in host during disease

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10
Q

What are the selective advantages of exotoxins to bacteria?

A

Train immune response
Enable biofilm formation
Enable attachment to host cells
Escape from phagosomes

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11
Q

What do the advantages of exotoxins to bacteria allow for?

A

Colonisation, niche establishment and carriage

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12
Q

What do haemolytic toxins do?

A

Cause cells to lyse by forming pores

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13
Q

What do phenol soluable modulins (PSM) do?

A

Aggregate lipid bilayer of host cells causing lysis

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14
Q

What chromosomal genes encode C. Difficile?

A

Ted A and ted B

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15
Q

What toxins are encoded by plasmids?

A

Bacillus anthracis

Tetanus

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16
Q

What toxins are encoded by lysogenic bacteriophages?

A

Scarlett fever and diphtheria

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17
Q

What are the types of toxin classification?

A

Type I, II and III

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18
Q

What are type I toxins?

A

Membrane acting toxins

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19
Q

What are type II toxins?

A

Membrane damaging

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20
Q

What are type III toxins?

A

Intracellular

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21
Q

What are the issues with classifying toxins by activity?

A

Many toxins have more than one type of activity

The better understood the mechanism, the less sense it makes

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22
Q

Where do type I toxins act from?

A

Outside the cell

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23
Q

How do type I toxins work?

A

Interfere with host cell signalling by inappropriate activation of host cell receptors

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24
Q

What do target receptors include?

A

Guanylyl cyclase
Adenyl cyclase
Rho proteins
Ras proteins

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25
What does guanylyl cyclase do?
Increase intracellular cGMP
26
What does adenyl cyclase do?
Increase intracellular cAMP
27
What is the mechanism by which the E. Coli stable heat toxin works?
``` Increases cGMP Increases chloride and bicarbonate transporters Inhibits sodium reuptake More water out of cells Diarrhoea ```
28
How do type II toxins work?
Insert channels into the host cell membrane
29
What are some examples of beta sheet toxins?
S. Aureus alpha toxin, gamma toxin and PVL
30
What are some examples of alpha helix toxins?
Diphtheria
31
What are some examples of type II enzymal damage toxins?
S. Aureus, beta haemolysin and PSM
32
What are the two types of type II toxins?
Receptor mediated | Receptor independant
33
What are the two components of type III toxins?
A and B
34
What are the B components of toxins responsible for?
Receptor binding and translocation
35
What are the A components of type III toxins?
The toxigenic (enzymatic) bit
36
What are the types of the A component?
``` ADP-ribosyl transferases Glucosyltransferase Deaminase Protease Adenyl cyclase ```
37
What are type III membrane acting toxins?
Intracellular
38
What do type III toxins act like?
A needle
39
What do type IV intracellular toxins act like?
A pump of toxins in the cell
40
What are exotoxins able to induce?
Inflammatory cytokine release
41
What are some examples of inflammatory cytokine release?
IL1, IL1 beta, TNF, IL6, interferon gamma and IL18
42
What are the mechanisms of a superantigen?
Non-specific bridging or the MHC class 2 and T cell receptor leading to cytokine production
43
How do superantigens cause non-specific bridging of MHCs?
Activation of the different inflammasome leading to IL1 beta and IL18 release
44
What are examples of different inflammasomes?
S. Aureus toxin A and PVL
45
How do superantigens work?
Antigen presenting cells -> lymph node -> T cell that processes the antigen that forms the specific antibody
46
What are toxins inactivated by?
Heat, formaldehyde or gluteraldehyde
47
What is an inactivated toxin called?
Toxoid
48
What is a toxoid?
Inactive proteins that are still highly immunogenic
49
What vaccines are based on toxoids?
Tetanus, diphtheria, pertussis
50
What illnesses are treated by administering preformed antibodies?
Diphtheria cuboxin (horse antibodies) Tetanus (pooled human Ig) Botulism (human antibodies)
51
What is the microbiology of clostridium difficile?
``` Gram positive Anaerobic Spore forming Toxin producing Carried asymptomatically in the gut ```
52
How many toxins does clostridium difficile produce?
3
53
Where do you tend to get clostridium difficile?
Hospitals
54
How is clostridium difficile spread?
Ingestion of spores that remain dormant in the environment
55
What are the risk factors for clostridium difficile?
Antibiotic use Age Antacids Prolonged hospital stay
56
What is the relevance for antibiotics with clostridium difficile?
Disrupt the microbial ecosystem in the gut which allows clostridium difficile overgrowth causing disease
57
What do antibiotics provide a competitive advantage to?
Spore forming macrobes over non-spore forming macrobes
58
What antibiotics are especially bad at disrupting the microbial ecosystem?
Quinolones Clindamycin Cephalosporins
59
What are the steps in Clostridium Difficile colonisation?
Toxins bind to specific host cell receptors are internalised Endosome acidification allows for inc CPD activity Pore formation in the endosome GTD release from the endosome to the host cell cytoplasm Rho GTPase inactivation by glucosylation
60
What are the downstream cytopathic effects of Clostridium Difficile colonisation?
Cytoskeleton breakdown Loss of cell-cell contacts Increased epithelial permeability
61
What are the downstream cytotoxic effects of Clostridium Difficile colonisation?
Activation of inflammasome Increase in reactive oxygen species (ROS) levels Induction of programmed cell death
62
What are symptoms of Clostridium Difficile disease?
Watery diarrhoea Dysentery Pseudomembranous colitis Toxic mega colon and peritonitis
63
What are the cytopathic and cytotoxic effects of Clostridium Difficile disease?
Patchy necrosis with neutrophil infiltration Epithelial ulcers Pseudomembranous leukocytes, fibrin, mucus and cell debris
64
What are the lab signs and symptoms of Clostridium Difficile disease?
Raised WBC count Detector of organisms and toxins in stool Defection of IgA/ B genes -> PCR Colonoscopy shows pseudomembranous colitis
65
How can you treat Clostridium Difficile disease?
Removal of offending antibiotic Give fidaxomicin, metronidazole or vancomycin Surgery (colectomy)
66
How do you treat recurrent Clostridium Difficile disease?
Faecal transplant
67
What causes VTEC disease?
Shigatoxin
68
How do you identify shigatoxin?
Growth on a sorbitol macconkey agar (SMAC) - doesnt ferment sorbitol so its clear
69
How is VTEC transmitted?
Predominantly by consumption of contaminated food and water Person-person particularly in childcare facilities and animal- person Low infectious dose
70
Where does VTEC come from?
Cows
71
What does low infectious dose mean?
Small amount -> outbreak
72
Where is the VTEC gene carried?
On a lysogenic virus
73
What are all the variations of the VTEC toxin?
Stx, stx1, ta1c, 1d2a, 2c, 2d
74
What type of toxin is the VTEC toxin?
Type III
75
What is the mechanism for VTEC binding?
Bind to receptor globotriasylceramide Gb3 or globotetraosylceramide Gb4 on host cell membrane Bound toxin internalised by endocytosis Carried by retrograde trafficking via the Golgi apparatus-> endoplasmic reticulum A subunit cleaved off by proteases
76
What happens once VTEC gets into the cytoplasm?
A1 and A2 dissociate
77
What does A2 do after it dissociates?
Binds to 285 RNA subunit - blocks protein synthesis