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Microbiology and Immunology > Bacterial Pathogens and Disease 1 (exotoxins) > Flashcards

Bacterial Pathogens and Disease 1 (exotoxins) Flashcards

1
Q

Define pathogen?

A

A microorganism capable of causing disease

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2
Q

Define pathogenicity?

A

Ability of an infectious agent to cause disease

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3
Q

Define virulence

A

Quantitative ability of agent to cause disease

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4
Q

Define toxigenicity

A

Ability of micro-organism to produce a toxin that contributes to the development of disease (not cause the disease)

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5
Q

What are the 4 mechanisms of virulence?

A

1) adherence factors
2) biofilms
3) invasion of host cells and tissues
4) toxins (endotoxins and exotoxins)

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6
Q

What are adherence factors?

A

proteins that allow bacteria to attach to surfaces

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7
Q

What is a biofilm?

A

allows cells to each other and to surfaces - allows to produce communities

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8
Q

When are endotoxins vs exotoxins released?

A

endotoxins - When the bacteria is killed

exotoxins - bacteria releases directly into environment

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9
Q

What are exotoxins?

A

Heterogeneous group of proteins produced and secreted by LIVING bacterial cells

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10
Q

What types of bacteria produces exotoxins?

A

Gram negative and gram positive bacteria

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11
Q

What effect does exotoxins have?

A

cause disease symptoms during disease

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12
Q

What else can exotoxins do apart from cause disease symptoms allowing exotoxins to be selectively advantageous component in bacteria?

A

Evade immune response
Enable biofilm formation
Enable attachment to host cells
Escape phagosome

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13
Q

Why are exotoxins good/bad for bacteria to release?

A

bad because causes disease = host may be evolutionary dead end = not advantageous

Good - allows colonisation, niche establishment and carriage

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14
Q

Where is staphylococcus aureus found?

A

In the nose - carried in humans asymptomatically

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15
Q

What toxins are released by S. aureus?

A

Haemolytic toxins and phenol soluble modulines (PSM)

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16
Q

cc

A
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17
Q

cc

A
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18
Q

What genes code for exotoxins? + examples

A

Most in extrachromosomal genes e.g. plasmids (tetanus toxin) and lysogenic bacteriophage (diptheria toxin)
Some in chromosomal genes e.g shiga toxin in shigella dysenteriae

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19
Q

What are the 3 types of exotoxins?

A

Type 1 - membrane acting toxins
Type 2 - membrane damaging toxins
Type 3 - intracellular toxins

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20
Q

Why is it hard to classify toxins into type1, 2 and 3?

A

Many toxin have more than one type of activity

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21
Q

What do membrane acting toxins (type 1) do?

A

Act from outside the cell to interfere with host cell signalling by inappropriate activation of host cell receptors

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22
Q

What does membrane acting toxins target? - 4 target mechanisms

A

Target receptors

  • guanylyl cyclase causes increase in intracellular cGMP
  • adenyl cyclase causes increase in intracellular cAMP
  • Rho proteins
  • Ras proteins
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23
Q

What is an example of type 1 toxin?

A

E coli stable heat toxin

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24
Q

Describe the action of e coli stable heat toxin (type 1 toxin)? step by step

A

1) Stable heat toxin binds to specific binding receptor (guanine cyclase receptor) on the membrane causing increase in intracellular cGMP
2) cGMP either
- acts on CFTR (cystic fibrosis transmembrane conductance regulator) to pump out Cl- and HCO3-
- increase cAMP levels which inhibit the pump which pumps out H+ and brings in Na+
3) Cl-, HCO3- and Na= all build up outside the cell, salt (NaCl) outside means water follows by osmosis leading to diarrhoea (disease symptom)

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25
What are the 2 types of type 2 (membrane damaging) toxins?
1) receptor mediated (insert channels into host cell membrane - beta sheet toxins and alpha helix toxins) 2) receptor independent (enzymatical damage to membrane)
26
Give an example fo receptor mediated type 2 toxin?
alpha toxin(beta sheet toxin), diptheria toxin (alpha helix toxin)
27
Give an example of enzymatical damage based type 2 toxin?
beta haemolysin and PSM's
28
What are the steps for receptor mediated toxin mechanism to cause damage to host cell membrane?
1) receptor binding (toxin binds to toxin specific receptor on host cell) 2) formation of defined pores made up of the toxin (polymerisation)
29
What are the steps for receptor independent toxin mediated mechanism to cause damage to host cell membrane?
1) toxin attaches to membrane 2) membrane disintegrates 3) formation of short lived pores
30
What are type 3 toxins?
Intracellular toxins - toxin is only active inside cell
31
How are the componets of intracellular toxins (type 3 toxins)?
Toxin is AB toxin (2 components) Component B allows exotoxin to bind to receptor and translocate into cell Component A is toxigenic(once inside the cell) and enzymatic
32
How many AB units are there in intracellular toxins?
Single ore multiple B unity
33
What is the toxin units for cholera exotoxin?
Cholera exotoxin is AB5 | 1 A component and 5 B components - multiple receptor binding units
34
What are the functions of component A of intracellular exotoxins?***
ADP - ribosonyl transferase - e.g exotoxin A Glucosyltransferases - e.g. TcdA and TcdB Deamidase Protease Adenylcyclase
35
What are the 3 types of intracellular toxins (type 3 endotoxins)?
AB toxins Type III Secretion and toxin injection Type IV Secretion and toxin injections
36
What is an example of a intracellular type 3 secretion and toxic injection exotoxin?
YopE in Yersinia species
37
What is the method for type 3 secretion and injection intracellular toxin?
Bacteria sticks a needle like structure into the membrane of host cell and injects its proteins directly in = NO RECEPTORS REQUIRED
38
Give an example of type IV secretion and toxin injection of intracellular exotoxins?
CagA in helicobacter pylori
39
Define superantigen
NON SPECIFIC BRIDGING of MHC class 2 and T cell receptor leading to cytokine production
40
How do exotoxins cause inflammation?
Induce inflammatory cytokine release | e.g. IL1, interferon, TNF
41
How do exotoxins induce inflammatory cytokine release?
Via superantigen mechanism OR | Via acivation of different inflammasome
42
How are toxoids formed?
Toxins inactivated using formaldehyde or glutaraldehyde
43
What are toxoids?
Incative proteins that are still highly immunogenic
44
What is the use of toxoids?
Basis of vaccine
45
Give examples of vaccines that are based off of toxoids?
Tetanus vaccine Diptheria Pertussis (accelular)
46
!!!! What is clostridium difficile?
Gram positive bacillus
47
Describe the microbiology / characteristics of clostridium difficiile
Anareobic, spore forming, toxin producing bacteria - can produce 3 toxins - present all the time asymptomatically in gut
48
What are the risk factors of for clostridium difficile?
Antiobiotic use Age Antacids Prolonged hospital stay
49
How does clostridium difficile spread?
Spores
50
Why does antibiotic use result in clostridium difficile cause disease?
Disrupts microbial ecosystem in the guy allowing competitive advantage to spore forming anaerobes over non spore forming anaerobes allow C. difficile colonisation
51
Which antibiotics increase risk of colonisation of C difficile?
2nd and 3rd generation cephalosporins Quinolones Clindamycin
52
What type of toxin is TcdA and TcdB?
Intracellular toxins (type 3 AB toxins)
53
What are the 3 toxins released by clostridium difficile?
Cytotoxin A - TcdA coded by tcdA gene Cytotoxin B - TcdB coded by tcdB gene Binary toxin - C diff transferase
54
What is component A of TcdA and TcdB in C diff?
Glycosylating enzyme
55
Outline the steps of how TcdA and TcdB cause cytotoxic and cytopathic effects?
1) TcdA/TcdB binds to specific host cell receptors 2) Toxin internalisation 3) endosome acidification 4) Pore formation in the endosome 5) GTD release from endosome to the host cell cytoplasm 6) Rho GTPases inactivation by glycosylation 7) Downstream effects within the host cell 8) cytopathic and cytotoxic effects
56
What are the cytopathic effects of TcdA/TcdB?
``` Cytoskeleton breaks down Loss of cell-cell contacts Increased epithelial permeability Destroy barrier Signal immune response ```
57
What are the cytotoxic effects of TcdA/TcdB?
Activation of inflammasome Increase in ROS levels Induction of programmed cell death
58
Describe the order in which clostridium difficile symptoms present themseles?
``` Asymptomatic Watery diarrhoea Dysentry Pseudomembrane colitis + patchy necrosis with neutrophil infiltration + epithelial ulcers Toxic megacolon and peritonitis ```
59
What are the clinical signs to diagnose C. difficile?
- Raised white cell count in blood (blood test) - Detection of organisms and toxins in stool (2 phase test) - Detection of tcdA and tcdB genes using PCR - Colonscopy - pseudomembranous colitis
60
What is the 2 phase test to diagnose C.difficile?
Detect organisms then toxins in stool sample 1) Glutamate dehydrogenase - detects if C.difficile organism is present 2) Toxin enzyme linked immunosorbent assay (ELISA) for TcdA and TcdB toxins
61
What is the treatment for C.difficile?
Treatment depends of severity/presence of surgical complications - remove offending antibiotic if possible - surgery (partial or total colectomy - recurrent - faecal transplant - to recolonise gut
62
What is VTEC?
Verocytotoxin escherichia coli disease or Shiga toxin (Stx) producing E coli (STEC)
63
How is STEC identified?
Growth on sorbitol MacConkey agar (SMac) because it doesn't ferment sorbitol
64
Where is VTEC found?
Naturally colonised in gastrointenstinal tracts of CATTLE
65
How is VTEC transmitted?
Consumption of contaminated food and water Person to person Animal to person
66
Why is tranmission of VTEC efficient?
Low infectious dose - very little needed to cause severe disease
67
What are the pathogenic toxins in VTEC?
Shiga like toxin (SLT), shigatoxin (Stx), verocytotoxin (VTEC)
68
What carries the shiga toxin varitation gene strands?
Gene carried on LYSOGENIC VIRUS
69
What type/class of toxin is shiga like toxin in VTEC? + explain the structure
Type 3 endotoxin - AB Enzymatic component A - N-glycosidase 5 B subunitys
70
Describe the mechanism for Stx in VTEC?
71
Describe how STEC leads to pathogenesis?
STEC adheres to epithelial cells of gut mucosa Stx transported from intestine to kidney and other tissues Stx binds to glomerular endothelial ells of kidney, cardiovascular and central nervous system KIDNEYS MOST AFFECTED Stx favours inflammation resulting in microvascular thrombosis and inhibition of fibrinolyis
72
What signs/other conditions arise when having STEC?
Abdominal cramps, water/bloody diarrhoea HAEMOLYTIC URAEMIC SYNDROME (anaemia, renal failure, thrombocytopaenia) also some neurological symptoms such as lethargy, sever headache, convulsions
73
How do you diagnose STEC?
Clinical signs and symptoms Stool culture grown on SMac PCR for Stx genes
74
What is the treatment for STEC?
Renal dialysis and blood product transfusion | - antibiotics have no role in this!!!

Microbiology and Immunology (31 decks)

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