Lecture 2 - Bacterial Pathogenesis Flashcards

1
Q

Differentiate between pathogens, opportunistic pathogens and normal flora

A

Pathogens: inherently cause disease

Opportunistic pathogens: only cause disease when given the chance (when host is immunosupressed, antacids etc.)

Normal flora: bacteria that are present in the gut under normal circumstances and do not cause adverse effects

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2
Q

Describe how a bacterium can be normal flora, opportunistic infection as well as a pathogen

A

Staphylococcus aureus
It is normally found on the skin - doesn’t cause disease.
However, when an individual is immunosupressed, it may cause disease

Toxin production in food can cause intoxication

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3
Q

What is a ‘virulent organism’?

A

This is an organism that is likely to cause disease

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4
Q

What is an ‘avirulent organism’?

A

This is an organism that won’t cause disease under normal circumstances (eg. normal physiology)

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5
Q

What are virulence determinants?

Give some examples

A
Characteristics that make an organism virulent
eg.
Pilli
Toxins
Capsules
Exzymes
Siderophores
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6
Q

What are some ‘opportunities’ for commensals to cause disease?

A

Immuno compromised individual
Antacids taken
Pathogen is moved (site specific)

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7
Q

Why are commensals important?

A

They contribute to:

  • immune system
  • metabolism
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8
Q

When does an infection go from asymptomatic to symptomatic?

A

After replication, when there is damage to host dissue

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9
Q

What is the generalised process of bacterial replication?

A
Colonisation
Penetration
Replication
Damage to host
Disease
Dissemination
Immunity
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10
Q

Describe how colonisation occurs

What are the two types of colonisation

A

Attachment:
• surface molecule (binding molecule / adhesin) + host receptor

Fimbrial / non - fimbrial

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11
Q

Why are epithelial cells said to be polarised?

A

Different ends of the cell have different expression of receptors

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12
Q

Why is polarisation of epithelial cells important?

A

Bacteria may need to damage epithelium to gain access to receptors

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13
Q

What are the two functions of fimbriae?

A
  • Adhesion

* Conjugation

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14
Q

What is the structure of fimbriae?

A

Hollow protein tube

Adhesin on the tip

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15
Q

Which part of a pilus binds to the host cells receptor?

A

The adhesin on the tip

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16
Q

How do we know fimbriae are involved in colonisation?

A
  • Can be used as antigen in vaccines for immunity

* Infection blocked by antibodies to fimbriae

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17
Q

How does a Urinary tract infection arise?

A

Bacteria from the rectum ‘ascend’ to cause an infection in the bladder

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18
Q

Who is more commonly affected by UTIs?

Why?

A

Women

Shorter urethra

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19
Q

Which bacterium is responsible for UTIs?

A

Uropathogenic E. coli

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20
Q

How do uropathogenic E. coli cause disease?

A
  1. ‘P’ fimbrial attachment to bladder epithelium
  2. Bacteria internalised
  3. Replicate to high levels
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21
Q

What is non-fimbrial adhesion?

A

This is when bacteria adhere to the host cell with molecules present on their cell wall
• glycocalyces (slime layer, capsule)
• teichoic acids

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22
Q

Give an example of non-fimbrial adhesion

A

Staphylococcus aureus adheres using Teichoic acids of the cell wall to the fibronectin and collagen of the host

Teichoic acid – Fibronectin

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23
Q

What are the two forms of glycocalyx?

How may they be differentiated?

A

Slime layer
Capsule

Slime layer can be washed away?

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24
Q

What is the function of glycocalyx?

A
  • Evasion of host defences by masking antigens

- Adhesion

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25
Q

What is a biofilm?

A

Any group of microorganisms in which cells stick to each other on a surface

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26
Q

Is penetration required for disease?

A

No,

some pathogens are extracellular

27
Q

Describe how bacteria penetrate cells

A

RME: receptor mediated endocytosis
• Invasins

Invasin or molecule on bacteria binds to a receptor on the host cell –> taken up into the cell

28
Q

How do bacteria spread between cells?

A

When bacteria penetrate a cell, they can alter the features of the cell, such an cellular junctions

Tight junctions become more leaky –> bacteria can spread more easily

29
Q

How does Pseudomonas cause disease, considering that it lacks the ability to invade

A

It can only invade when there is damage to the epithelium - such as in burns victims

30
Q

Where are the different locations where bacterial replication can occur?

A
  1. On cells (extracellularly)
  2. Intracellularly
    • endosome
    • cytoplasm
31
Q

What are the pros and cons of the different locations of intracellular bacterial replication?

A

Endosome:

pro: more protection from molecules in the cytosol
con: less nutrients

and vice versa

32
Q

True of false: penetration and replication are essential for infectious disease?

A

False
Only replication is essential

Bacteria can cause disease extracellularly

33
Q

Describe the features of the bacterial growth curve

A

Lag phase:
Log phase: exponential growth of bacteria, diving by binary fission
Plateau: stable numbers
Decline: due to competition for resources and quroum sensing

34
Q

True or false?

There can be many different species of bacteria in a biofilm

A

True

Normally not just one species

35
Q

What do biofilms contain?

A

Bacteria
Glycocalyces
Metabolites

These hold the bacteria together

36
Q

What controls the formation of a biofilm?

A

Quorum sensing

37
Q

What is quorum sensing?

A

Recognition of bacteria within a colony by chemical signals released by neighbouring bacteria

38
Q

What happens when there are sufficient numbers of bacteria?

A

A quorum

The signal takes effect

39
Q

What are the two types of signal in quorum sensing?

A

Generic

Specific

40
Q

What are biofilms normally associated with?

A

Chronic infection

41
Q

What sort of genes do signals from quroum sensing regulate?

A

Replication
Biofilm production
Virulence determinants

42
Q

What happens to metabolic activity in a biofilm?

A

Reduced metabolic activity, because the bacteria can rely on their neighbours and become more efficient

43
Q

Why are microfilms bad?

A
  • Increased expression of virulence determinants
  • Protection form host defences
  • Greater opportunity for gene transfer
44
Q

When does an infection pass from subclinical to disease?

A

Subclinical: numbers below the threshold
Disease: numbers above a certain threshold

45
Q

How may physical barriers be subverted by bacteria?

A

Trauma

Surgury

46
Q

How may the complement system by avoided by bacteria?

A

Enzymes that destroy C’

47
Q

How do bacteria evade phagocytes?

A
  • Capsules
  • Escape phagosome
  • Survive in phagosome
  • Kill phagocytes
48
Q

How do bacteria evade Ab?

A

Enzymatic destruction

49
Q

How do bacteria evade APCs?

A

Down regulate MHC expression to reduce the efficiency of APCs

50
Q

What are the three ways that bacteria can cause damage to the host?

A

Endotoxin
Exotoxin
Immunopathology

51
Q

In general, how does exotoxin work?

A
  1. Produced by bacteria
  2. Gets into host cell (B subunit)
  3. Cytotonic, cytotoxinc (A subunit)
52
Q

When is endotoxin primarily produced?

A

When cells die

53
Q

What is the structure of endotoxin?

A

Polysaccharide

Lipid A

54
Q

What is the effect of LPS?

A
  • Activates the alternate complement pathway

* Binds and activates macrophages and neutrophils by PRRs

55
Q

Describe how bacteria disseminate

Give some examples

A
  1. They produce compounds that break down:
    • intercellular matrices
    • cells

For example:
• Hyaluronidase
• collagenases
• elastases

  1. Use host physiology
    • blood
    • nervous system
56
Q

Describe how bacteria can use the host’s physiology to disseminate

A

Neuronal transport

Blood circulation
• intra / extracellular

57
Q

Why is infection a race? Who are the competitors?

A

It is a race:
Pathogen vs. Host’s immune system

Immune system wins: recovery
Pathogen wins: loss of function, death
Pathogen partially wins: chronic infection, latency

58
Q

How can we affect the outcome of ‘The Race’?

A
  • Maintain physical barriers
  • Maintain innate IR
  • Maintain adaptive IR
  • Reduce virulence of organism
  • Reduce n° of organisms
59
Q

What are some features of normal flora?

A
  • mutualistic relationship with host (don’t cause disease)
  • cause disease if moved to another area
  • occupy the niche to prevent pathogens colonising
  • contribute to immune system and metabolism
  • Can be transient / stable
60
Q
TRUE / FALSE:
In Biofilms there is increased:
• metabolic activity
• expression of virulence determinants
• replication
• gene transfer
• protection from host and antibiotics
A
  • metabolic activity FALSE
  • expression of virulence determinants TRUE
  • replication TRUE
  • gene transfer TRUE
  • protection TRUE
61
Q

How do bacteria kill phagocytes?

A

Leucocidins

62
Q

Draw a typical AB5 exotoxin

A

Slide 26

63
Q

When is endotoxin mainly produced?

A

When G- bacteria die