Fungal Pathogens Flashcards

(55 cards)

1
Q

What are yeasts?

A

Unicellular oval shaped fungi

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2
Q

What are moulds?

A

Typically multicellular fungi that form a network of thread-like structures called hyphae.

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3
Q

What are 2 examples of yeasts?

A

Candida spp. (generally)
Cryptococcus spp.

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4
Q

What are 2 examples of moulds?

A

Aspergillus spp.
Mucor spp.

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5
Q

What is the name for a fungi that can switch between yeast and mould?

A

Dimorphic fungi

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6
Q

What are 2 examples of dimorphic fungi?

A

Histoplasma
Candida albicans

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7
Q

Why are fungi clinically important?

A
  • 1.5 million deaths/year (WHO 2023); comparable or exceeding deaths from malaria or TB
  • Emerging threats like Candida auris and Aspergillus fumigatus
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8
Q

What causes dimorphic fungi to change morphology?

A

Primarily temperature, but other factors like pH and nutrient availability can also induce change

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9
Q

Generally, what temperatures induce are dimorphic fungi yeast, and mould?

A

Yeast - 37C (human body temp)
Mould - 25C (room temp)

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10
Q

How do yeasts and moulds grow respectively?

A

Yeasts - budding
Moulds - apical extension

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11
Q

What is something that in unique to fungal pathogens that makes it difficult to find effective antifungals?

A

As eukaryotic pathogens, they share many similarities with host cells, making the development of effective and safe anti fungals difficult

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12
Q

What percentage of global infectious disease funding do fungal pathogens receive?

A

Less than 1.5%

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13
Q

What is morphological switching in Candida albicans and why is it important?

A

The ability to switch between yeast and hyphal forms. Hyphae penetrate tissues and escape phagocytosis, enhancing virulence.

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14
Q

Do moulds like Aspergillus fumigatus undergo morphological switching?

A

No — they grow as filamentous hyphae. Their virulence depends on other factors like spore formation and toxin production.

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15
Q

Which fungi produce toxins and what do these toxins do?

A

Moulds like Aspergillus produce gliotoxin, which suppresses the immune system by:

  • Inhibiting neutrophil function
  • Inducing host cell apoptosis
  • Blocking reactive oxygen species (ROS) production
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16
Q

What are the main virulence factors used by Candida spp.?

A

Morphological switching (C. albicans)
Adhesins
Biofilm formation
Release of hydrolytic enzymes
Phenotypic switching
B-glucan masking

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17
Q

What are the main virulence factors used by Aspergillus spp.?

A

Spore formation
Gliotoxin production
Release of hydrolytic enzymes
Biofilm formation

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18
Q

What are the main virulence factors used by Cryptococcus spp.?

A

Polysaccharide capsule
Melanin production
Titan cell formation
Phenotypic switching
CNS tropism

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19
Q

What are Candida adhesins?

A

Fungal surface Als proteins. Important for:
- Adhesion to epithelial and endothelial cells (colonisation), as well as abiotic surfaces (e.g. catheters)
- Formation of biofilms

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20
Q

What enzymes does Candida secrete, and what do they do?

A

Hydrolytic enzymes like:
- Aspartyl proteases (degrade immune molecules)
- Phospholipases (disrupts host cell membranes; facilitates invasion)

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21
Q

What enzymes does Aspergillus secrete, and what do they do?

A

Hydrolytic enzymes like:
- Proteases and elastases, which degrade host extracellular matrix (e.g. elastin in lung tissue)
- Aids in lung and blood vessel colonisation

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22
Q

What are the spores formed by Aspergillus?

A

Spores are called Conidia, and they are a key way in which Aspergillus can spread:
- Tiny in size (allow to bypass upper respiratory defences straight to alveoli)
- Surface rodlet proteins + melanin protect against immune defences
- Once in host lung, they can germinate into hyphae; allow for invasion of tissue

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23
Q

What is the Cryptococcus polysaccharide capsule?

A

A polysaccharide outer layer that protects from phagocytosis and aids in immune evasion

24
Q

What is the role of melanin production by Cryptococcus spp.?

A

Melanin works to neutralise reactive oxygen species, protecting the fungi from oxidative damage

25
What is an important mineral that is required by fungi for survival?
Iron
26
How does Candida spp. uptake iron?
Uses reductive uptake systems to scavenge iron from host sources
27
How does Aspergillus spp. uptake iron?
By using siderophores, which are high affinity iron chelators for uptake in iron-limited environments
28
How does Cryptococcus spp. uptake iron?
Using a high-affinity reductive uptake system. It can also use siderophores produced by other microbes (although it doesn't use its own)
29
What are some key structural components of fungi?
B-glucans (cell wall) Chitin (cell wall) Ergosterol (cell membrane)
30
What is the key role of ergosterol in fungi?
Regulating fungal cell membrane fluidity and permeability
31
What are the 4 classes of antifungals?
- Polyenes - Azoles - Echinocandins - Allylamines However there as been use of pyrimidine analogues as an anti fungal treatment
32
What is an example of a polyenes?
Amphotericin B
33
What do polyenes target?
They bind to ergosterol in the fungal membrane, creating pores that cause cell content to leak out- cell death
34
What is an example of an azole?
Fluconazole
35
What do azoles target?
They target the ERG11 enzyme, which is crucial for the synthesis of ergosterol-inhibiting cell growth and disrupting membrane integrity
36
What is an example of an echonocandin?
Caspofungin
37
What do echinocandins target?
They target glucan synthase, which is crucial for the synthesis of the B-glucan cell wall- weakens the cell wall, leading to cell death
38
What is an example of an allylamine?
Terbinafine
39
What do allylamines target?
They target squalene epoxidase, an enzyme involved in ergosterol synthesis- the toxic accumulation of squalene leads to cell death
40
What is an example of a pyrimidine analogue?
Flucytosine
41
What do pyrimidine analogues target?
They disrupt DNA and RNA synthesis within the fungal cell
42
What are the two action classes of antifungals?
Fungistatic (inhibits fungal growth Fungicidal (kills fungi)
43
For each of the previously discussed fungi, say whether each is fungistatic or fungicidal?
- Polyenes = fungicidal - Azoles = fungistatic - Echinocandins = fungicidal - Allylamines = fungicidal - Pyrimidine analogous = fungistatic
44
For what antifungals are biofilms particularly an issue?
Azoles and echinocandins
45
How do target gene mutations contribute to echinocandin resistance?
Mutations in the FKS1 gene encoding β-glucan synthase reduce the binding of echinocandins, leading to resistance.
46
What role do cell wall salvage pathways play in echinocandin resistance?
Upregulation of chitin synthesis and other cell wall salvage pathways compensates for the loss of β-glucan, maintaining cell wall integrity and contributing to resistance.
47
How do molecular chaperones contribute to echinocandin resistance?
Hsp90 and its client proteins are involved in stress response, enhancing fungal survival under echinocandin-induced stress.
48
How do target gene mutations and overexpression contribute to azole resistance?
Mutations in the ERG11 gene encoding lanosterol 14-α-demethylase, and overexpression of ERG11, reduce drug binding and increase production of the target enzyme, leading to resistance.
49
What role do efflux pumps play in azole resistance?
Upregulation of ABC and MF transporters increases the expulsion of azole drugs from the cell, reducing intracellular concentration and effectiveness.
50
How do loss-of-function mutations in ERG3 contribute to azole resistance?
Mutations in ERG3 prevent the accumulation of toxic sterol intermediates, allowing fungi to resist azoles by avoiding toxic effects.
51
How do aneuploidies contribute to azole resistance?
Duplication of chromosome segments (e.g., isochromosome 5L) increases the dosage of ERG11 and efflux pump genes, enhancing resistance.
52
How do ergosterol biosynthesis mutations contribute to polyene resistance?
Mutations in genes involved in ergosterol biosynthesis lead to the depletion of ergosterol and accumulation of alternative sterols, reducing polyene binding and effectiveness.
53
How do molecular chaperones contribute to polyene resistance?
Hsp90-dependent stress responses enhance fungal survival under polyene-induced stress.
54
Which grow faster out of moulds and yeasts?
Moulds
55
What are 4 diagnosis techniques for fungal infections?
- Staining and microscopy - Culturing - Molecular techniques (PCR) - Serological antigen/antibody tests