introduction to fungi

Question 1

what type of pathogens are fungi

Answer 1

they are opportunistic and tend to cause problems in humans when the individual is immunosuppressed
many fungi are commensal organisms but maintaining the balance is important in preventing infection

Question 2

examples of situations where fungi can cause infection

Answer 2

neutropenic host - low neutrophil levels

leukamia - chronic immunosuppression

Question 3

what is a fungus

Answer 3

a chemo-organotrophic eukaryote that lacks chlorophyll and forms spores, its cell wall contains polysaccharides (often chitin or glucan) and it absorbs nutrients. Its membrane contains ergosterol as the major sterol (steroid based alcohol). Classification is principally based on morphology (informally the major types are referred to as moulds, yeasts or mushrooms.

Question 4

yeasts

Answer 4

fungi that favour a unicellular habit (single cellular and produce pseudo hyphae, go through the asexual process of budding to reproduce)

Question 5

examples of diseases caused by fungi

Answer 5

Fungi are a significant cause of non-fatal diseases
Athletes foot: caused by Epidermophyton, Microsporum and Trichophyton spp.
Thrush: caused by Candida spp.
Pityriasis versicolor: caused by Malassezia spp.

Question 6

dermatophyte virulence factor

Answer 6

enzyme(s) that degrade and utilise keratin as a nutrient source
Diseases caused by the dermatophytes - ringworm infections, usually called tinea…

Question 7

dermatophytosis

Answer 7

Causative agents: Epidermophyton, Microsporum and Trichophyton spp.
Moulds with a predilection to degrade keratin as a nutrient source - live in the skin

Question 8

Pityriasis versicolor

Answer 8

causative agents - Malassezia spp. Yeasts that also form hyphae in infected skin, causes asymptomatic white patches to develop on the skin (don’t cause disease), causes demelanisation

Question 9

examples of fatal diseases caused by fungi

Answer 9

• Candida species infect deep organs of patients with various types of immune dysfunction (e.g. after abdominal surgery, burns etc (cases often in ICU))
  Aspergillus spp: infect deep organs of patients undergoing e.g. chemotherapy, stem cell transplant

Question 10

host factors that contribute to the pathogenicity of fungal infections

Answer 10

• Favourable micro-environments (warm, moist areas) encourage growth of fungi on skin and mucous membranes
  
  • Broad spectrum antibacterial agents reduce competition for epithelial colonisation sites in the gut
    Immunosuppression of all types may create a window of opportunity for fungal invasion

Question 11

immunosuppresion of host defences

Answer 11

• Latrogenic: causes due to medical treatment of other conditions e.g. steroids, anti-cancer chemotherapy, solid-organ transplantation
  
  • Disease processes: AIDS, leukaemia, endocrinopathies
    Combinations of both

Question 12

candida infections

Answer 12

C. albicans - oral 
C. tropicalis - vaginal 
C. glabrata - skin 
C. krusei - nail 
C. parapsilosis - oesophageal 
C. auris - uti 
other - disseminated infections

Question 13

disseminatin of Candida

Answer 13

High risk area for pathogens to become a systemic issue in immunocompromised individuals
Antiobiotics remove bacteria, allows yeast to take hold, multiply and form biofilms
Surgical insult allows yeast to enter the blood stream

Question 14

clinical examples of candida infections

Answer 14

Oral thrush - white sheen on the tongue, due to dead cells which were killed by invading candida

Nappy rash: white is due to dead epithelial cells due to invading fungus

Thrush

Candida intertrigo: infection of the skin where there are folds e.g. in between the fingers,

Candida onychomycosis: infections on the nail, hyphae extend into the nail bed

Chronic mucocutaneous Candida infection: can arise in individuals with an unusual combination of endocrine and immune dysfunction (autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy - APECED)

Question 15

aspergillosis

Answer 15

Causative species: aspergillus fumigatis (main cause), aspergillus flavus, aspergillus nidulans (in CGD patients), Aspergillus lentulus, other species
Most species exist where organic material is breaking down e.g. compost heap
Real problem regarding lung diseases as it is so easily inhaled
Types of disease: simple asthma, asthma with eosinophilia, aspergilloma, invasive bronchopulmonary aspergillosis, disseminated aspergillosis
Route of infection: inhalation of conidia
A. Fumigatus infects by inhalation of condida which germinate to hyphae in the lung tissue, it is angioinvasive (invades walls of blood vessels)

Invasive pulmonary aspergillosis

- Mainly associated with haematological malignancy 
- Specific diagnosis is very difficult

Question 16

cryptococcosis

Answer 16

yeasts with a capsule
C. neoformans - pulmonary
C. gattii - meningitis

Question 17

damage - response interaction

Answer 17

Too much and too little immunity is bad
Too strong an immune system leads to autoimmunity, to little immunity means the body can’t fight off the pathogenic fungi so they are able to multiply and cause disease

Question 18

diagnostic methods in mycology

Answer 18

Direct detection (histopatholohy, high res CT)
direct smear
Growth on selective medium E.g. chromAgar allows selection on agar plates, colour difference is due to changes in pH of individual pathogens (allows assessment of which candida species are present in an infected tissue)
○ Detection of circulating fungal antigens
○ Detection of circulating antibodies to fungi
PCR for fungal DNA

Question 19

antifungals

Answer 19

target key differences in the cell walls of fungi

- sterols (triazoles and allyamines), wall (echinocandins), membrane (polyenes), DNA synthesis (flucytosine)

Question 20

problems with antifungals

Answer 20

spectrum of activity, static or cidal, IV vs oral, toxicity, resistance, cost

Question 21

antifungal agents

Answer 21

polyenes, azoles, echoncandins

Question 22

polyenes

Answer 22

amphotericin B - fungistatic (doesn’t remove the infection completely)(topical, IV, lozenge, ointment, oral suspension)
Nystatin (topical, pastille, oral suspension)

Question 23

azoles

Answer 23

Clotrimazole, miconazole, several others (topical)
Fluconazole, itraconazole, voriconazole (oral and/or IV)
Posaconazole (oral)

Question 24

echonocandins

Answer 24

Anidulafungin, caspofungin, micafungin (IV)

Question 25

drug resistance in fungi

Answer 25

• Global emergence of invasive infections cause by the multidrug-resistant yeast Candida auris
  
  • Potentially a massive issue to be aware of
    Highlights the importance of effective antifungal drugs