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Pathogens and Pathogenicity > The Pathogenicity of Fungi - Candida albicans > Flashcards

The Pathogenicity of Fungi - Candida albicans Flashcards

1
Q

What two types of infection are caused by c. albicans?

A
  1. Superficial infections - oral, vaginal, skin infections

2. Systemic infections - kidney, liver

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2
Q

Where do C. albicans live commensally within the body?

A

Oral cavity, skin, urinogenital tract, gastrointestinal tract and to a lesser extent the respiratory system.

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3
Q

What is the disease caused by C. albican infection of the oral cavity?

A

Oral candidiasis

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4
Q

Who is at risk of developing oral candidiasis?

A
  • Immunocompromised individuals such as HIV patients.
  • use of dentures
  • old age
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5
Q

What disease is caused by c. albican infection of the vula and vagina?

A

Vulvovaginal candidiasis

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6
Q

What five factors predispose an individual to vulvovaginal candidiasis?

A
  • Diabetes Mellitus
  • Antibiotic use
  • Oral contraception
  • Pregnancy
  • Hormone therapy
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7
Q

What causes C. albicans to develop from a non-lethal superficial infection to a lethal systemic infection?

5 causes listed

A
  1. Neutropenia
  2. Damage to gastrointestinal mucosa.
  3. Central venous catheters allowing direct access to the bloodstream
  4. Broad spectrum antibacterials allowing for overgrowth of the fungus
  5. Gastrointestinal surgery which disrupts mucosal barrier
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8
Q

Mention a few known virulence factors of C. albicans.

A
  • Morphological transition between yeast and hyphal forms
  • Adhesins and invasins present on the C. albican cell surface
  • Thigmotropism (movement in response to stimuli)
  • Biofilm formation
  • Phenotypic switching
  • Secretion of hydrolytic enzymes
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9
Q

What factors cause C. albicans to grow in the yeast form in vitro?

A

Low pH is known to induce preferential growth of the yeast form as well as many ‘non-stressful’ conditions.

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10
Q

What factors cause C. albicans to grow in the hyphal form in vitro?

A
  • High pH
  • starvation
  • Presence of serum
  • Presence of N-acetylglucosamine
  • Physiological temperature
  • Presence of carbon dioxide
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11
Q

What is the term given to the transitioning ability of C. albicans between its yeast and hyphal forms?

A

Dimorphism

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12
Q

What are the benefits to the C. albican of the hyphal form?

A

Increased invasion of host cells

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13
Q

Which form is associated with dissemination

A

The yeast form

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14
Q

Why is the hyphal form of C. albicans more invasive?

A

Increased expression and presence of adhesin molecules associated with C. albican attachment to the host cell.

Additionaly entry mechanisms

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15
Q

Name a few adhesin molecules associated with the hyphal form of C. albicans.

A

Als3, Hwp1

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16
Q

What does C. albican bind to via adhesin molecules

A

Mainly important for attachment to host cells, but also attach to other C. albican cells, other microorganism cells and abiotic structures.

17
Q

Name other adhesins not asssociated with either form of C. albicans specifically and mention their host cell ligands.

A
  1. Glucan -> Vitronectin
  2. Chitin -> Unknown
  3. Mannan structures - Macrophage mannose receptor
18
Q

How does C. albicans enter host cells upon attachment?

A

Endocytosis thought to be by clathrin dependent mechanism

or

Active penetration

19
Q

What is required for endocytosis of C. albicans to occur?

A

Invasins that mediate binding to host ligands to trigger the engulfment of fungal cells

20
Q

Give an example of an invasin and its host cell ligand binding partner.

A

Als3
Ssa1

Both bind to E-Cadherin

21
Q

What is the consequence of mutation of these two invasins?

A

Reduced attachment and entry into host cells and reduced virulence of infection.

22
Q

What is required for C. albicans to enter the host cell via active penetration?

A

The hyphal form.

+Secreion of aspartic proteases is thought to also contribute to invasion.

23
Q

What is the purpose of biofilm formation?

A

Biofilms are more resistant to antimicrobial agents and host immune response

24
Q

What 5 stages are associated with biofilm formation?

A
  1. Adherance of yeast
  2. Proliferation of yeast cells
  3. Formation of hyphal cells in the upper part of the biofilm
  4. Accumulation of extracellular matrix material
  5. Dispersion of yeast cells from biofilm complex
25
Q

What makes a biofilm aid in resistance to antimicrobials?

A
  • Increased expression of drug efflux pumps

Metabolic plasticity

Complex architecture of biofilms and matrix providing a mechanical barrier.

26
Q

What is the importance of thigmotropism?

A

Encountering a surface (contact sensing) stimulates C. albicans to convert to the hyphal form of increased virulence.

27
Q

What is the importance of secreted hydrolases?

A

Secretion of hydrolases aids in the process of active penetration to enter host cells.

28
Q

What 3 forms of secreted hydrolases are secreted?

A
  1. Proteases
  2. Phospholipases
  3. Lipases
29
Q

How does C. albican detect changes in pH

A

Membrane receptors Dfg16 and Rim21

30
Q

How does C. albicans adapt to pH changes?

A

Via the Rim101 signal cascade to activate necessary genes

Hyphal formation

If low pH: Neutralising its environment via the uptake of amino acids, cleavage of amine molecules to form ammonia, export of ammonia via Ato (ammonia transport outward) transporters.

31
Q

How does the metabolic plasticity of C. albicans aid in its pathogenesis?

A

The ideal nutrient source for C. albicans is glucose however this nutrient is not always readily available in its environment (e.g. upon ingestion by a macrophage). Therefore in a state of starvation, C. albicans switches from glycolysis to gluconeogenesis allowing for the use of lipids and amino acids as nutrient sources.

Therefore by being able to utilise a range of nutrient sources, Candida albicans can result in systemic infections of virtually every organ in the body.

32
Q

How does C. albicans escape the immune response?

A

Upon ingestion by a macrophage, morphology into the hyphal state has been shown to pierce macrophages to allow escape.

33
Q

How does C. albicans tolerate temperature stresses?

A

HSP release preventing protein unfolding and aggregation

34
Q

How does C. albicans tolerate osmotic stress?

A

Release of glycerol to counteract the chemical gradient resulting in loss of water.

35
Q

How does C. albicans tolerate ROS?

A

The release of substances capable of detoxification of ROS such as Catalase Cta1 and superoxide dismutase Sod1.

36
Q

How does C. albicans tolerate RNS and where would it encounter RNS?

A

Within neutrophils:

Flavohemoglobin-related protein Yhb1 released detoxifies RNA

37
Q

What pathway is activated inr esponse to these aforementioned stress signals to elicit adaptations?

A

Mitogen activated protein kinase pathways (MAP kinase pathway):

  1. Mkc1- MAP kinase pathway
  2. Hog1 MAP kinase pathway
  3. Cek1 MAP kinase pathway

Pathogens and Pathogenicity (17 decks)

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