Fungal Pathogens II Flashcards

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1
Q

Damage from disease can occur in 2 ways

A
  1. Direct damage from microorganism (e.g. not enough host response)
  2. Damage from host immune over-reaction
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2
Q

Damage to the host will have a

A

Disease threshold

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3
Q

Candida infection can cause both

A
Direct damage (systemic infection)
Host overreaction (cutaneous infection)
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4
Q

Identification of virulence factors

A

Reverse genetics - candidate gene approach (most common) ‘is this gene important in virulence?’
Forward genetics - genome wide approach

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5
Q

Confirmation of virulence factors

A

Koch’s molecular postulates

  1. Disrupt target gene to create mutant strain
  2. Demonstrate attenuated virulence of mutant
  3. Reintroduce gene to restore virulence
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6
Q

The status of the host is very important in

A

Candida infection

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7
Q

Stages of candida infection

A
  1. Adhesion and colonisation
  2. Epithelial penetration
  3. Vascular dissemination
  4. Endothelial colonisation and penetration
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8
Q

C albicans virulence is

A

Multi factorial

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9
Q

Candida virulence factors

A
  1. Adhesion to host surfaces
  2. Invasion of epithelial layers
  3. Penetration beyond epithelia
  4. Obtaining nutrients
  5. Opposing host defences
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10
Q

Host defences

A
  1. Flushing mechanisms
  2. Molecular recognition
  3. Phagocytosis and killing
  4. Immune response
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11
Q

Characteristics of candida

A
  1. Diploid (8 chromosomes)
  2. Largely asexual
  3. Polymorphic
  4. CUG codon
  5. Causes candidosis
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12
Q

C albicans polymorphisms

A
  1. Yeast
  2. Pseudohyphae
  3. Hyphae
  4. Opaque
  5. Chlamydospore
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13
Q

What causes hyphal growth

A
High temps above 35
Neutral pH 6.5
High pCO2 low pO2
N/C starvation
Matrix embedded growth
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14
Q

What causes yeast growth

A

Low temps below 35
Acidic pH
Nutritious environment NH4+ ions

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15
Q

What also plays a role in morphogensis between yeast and hyphae?

A

Quorum sensing

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16
Q

Quorum sensing tells candida in high cell densities

A

To grow as a yeast

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17
Q

Quorum sensing tells candida in low cell densities

A

To grow as hyphae

18
Q

Virulence of hyphal morphology

A

Tissue penetration

19
Q

Virulence of yeast morphology

A

Vascular dissemination

20
Q

The ability to switch morphologies in candida is key to its

A

Virulence

21
Q

Yeast or hyphae morphology locked mutants

A

Show attenuated virulence

22
Q

Damage to the host is mainly through which form of candida?

A

Hyphal

23
Q

Hyphae have both direct and indirect roles in

A

Virulence

24
Q

Direct roles of hyphae in virulence

A

Invasion
Thigmotropism
Escape from phagocytes

25
Q

Indirect roles of hyphae in virulence

A

Through genes co regulated with morphogenesis (eg toxins)

26
Q

Candida lysin is a toxin that is only produced by

A

Hyphal cells

27
Q

What toxin does hyphal candida produce

A

Candida lysin

28
Q

When candida yeast cells are engulfed by a phagocyte

A

They switch to hyphal morphology and erupt from the phagocyte

29
Q

Candida is very ‘sticky’ and can adhere to

A

Epithelium/Endothelium
Medical devices
Biofilms
Bacteria

30
Q

How does candida adhere to surfaces?

A

Cell surface Manno proteins

glycosylated

31
Q

Which gene family is used in candida adherence?

A

ALS family

Agglutinin like sequence family of cell wall proteins

32
Q

Als3

A

ALS protein

Especially important in adherence

33
Q

Candida invasion is done through 2 routes

A
  1. Induced endocytosis

2. Active penetration

34
Q

Induced endocytosis

A

Fungal ‘invasin’ interacts with cell surface proteins

Fungus is engulfed - ‘zipper like’

35
Q

Active penetration

A

Directly through or inbetween cells

  1. Physical force from directional growth and turgor pressure
  2. Secreted hydrolytic enzymes damage host tissue
36
Q

Candida biofilms are

A

Structured assemblies encased in an extracellular matrix

37
Q

Biofilms are inherently

A

Resistant

To host defences and drug therapy

38
Q

Stages of biofilm development

A I M D

A

A - ttachment
I - nitiation
M - aturation
D - ispersal

39
Q

Main type of hydrolytic enzyme produced by candida

A

Aspartic proteinases

40
Q

Candida has strategies to uptake which nutrient from the host?

A

Iron

41
Q

Candida iron uptake methods

A
  1. Reductive pathway (rips iron out of ferritin)
  2. Siderophore uptake (iron carriers produced by other microbes in vicinity)
  3. Haemoglobin destruction (binds to Hb and and tears out the haem to access iron)
42
Q

Candida can deal with the stresses of an immune response by

A

Switching to hyphal form