human fungal infections

Question 1

how do fungi cause harm - mycotoxicoses

Answer 1

mycotoxicoses
- reaction to ingested or inhaled mycotoxin - poisoning
these are small organic metabolites that are produced by fungi and are toxic

examples of fungal secondary metabolites include penicillin, the statins, psilocybin, aflatoxin, gliotoxin

Question 2

symtpoms of mycotoxin poisoning

Answer 2

breathing problems, dizziness, hallucination, severe vomiting, diarrhoea, dehydration, hepatic and renal failure

Question 3

how else do fungi cause harm

Answer 3

allergies - hypersensitivity to fungal components

mycoses - fungal infections

Question 4

fungal allergies - a world wide problem

Answer 4

inhalation of/ mcontact with fungal spores may induce a wide range of allergic disease:
- rhinitis
- dermatitis
- asthma
- allergic bronchopulmonary aspergillosis

allergic responses differ by individual and by species

Question 5

how are mycoses classified

Answer 5

by the level of tissue affected

Question 6

skin mycosis

Answer 6

Superfical mycoses - mostly in the tropics and are restricted to the outer surface of the hair and the skin
e.g. T.rubrum

Cutaneous mycoses - attack the non living tissue of the skin hair nails and they grow just below the zone where the carotene is deposited
e.g. onychomycosis

subcutaneous mycoses - that are caused by infection in wounds in
the skin, so they are deeper.

Question 7

system (deep)/ invasive - mycoses

Answer 7

brain, lungs, heart, liver, spleen, kidney
C.albicans

Question 8

how many fungal species can cause disease

Answer 8

400 fungal species that are able to cause disease in humans and domestic animals

60 specific to humans

Question 9

invasive mycoses - fungal shapes

Answer 9

fungal shapes vary dramatically and importantly, this affects every apsect of their interactions with the human host

Question 10

yeast

Answer 10

single celled fungal morphotypes

Candida albicans - budding yeast

cryptococcus neoformans - encapsulated yeast
- a capsule is a thick polysaccharide cell wall referred to as the capsule - The capsule is protecting the fungus and it’s one of the major virulence factor of the fungus itself.

Question 11

yeast - C.albicans

Answer 11

Can form filaments of hyphae - important for its ability to cause damage to infiltrate in the tissue
C.albicans can differentiate into pseudohyphal and hyphal forms in response to: pH, nutrient limitation, serum

Question 12

moulds

Answer 12

sporulating fungi distribute spores via air currents to inhabit new food sources

Aspergillus niger - filamentous fungus

Question 13

in favourable conditions what do mould spores germinate into

Answer 13

in favourable conditions, these spores germinate into hyphae, which branch and at their ends forms structures bearing the spores, named conidiophores.

Question 14

what is a mycelium

Answer 14

a fungal colony composed of multiple branched hyphae

Question 15

dimorphic fungi

Answer 15

-a bit less studied because they are more difficult to manipulate
-This is a primary fungi
They are present in two complete different shapes depending on the temperature that they encounter.

Question 16

opportunistic pathogens

Answer 16

requires a compromised host to establish infection
- ubiquitous

e.g. cryptococcus neoformans
Candida albicans

Question 17

primary/true pathogens

Answer 17

able to establish infection in a normal host
- well-defined geographical areas
e.g. Histoplasma capsulatum

Question 18

factors impacting disease outcomes

Answer 18

1. circumstantial
   - how frequently do the host and pathogen come into contact with each other
2. organism - related
   - does the pathogen possess specific virulence factors which promote survival in the host
3. host related
   - are the immune defences of the host impaired

Question 19

immune response of fungal species

Answer 19

immune response varies by fungal species and morphotype encountered
- the relative importance of innate and adaptive immunity differs by fungal species and anatomical site

Question 20

candida (mucosal infection) risk factor

Answer 20

impaired cell-mediated immunity (e.g. AIDs)

Question 21

candida (disseminated infection) risk factor

Answer 21

• breach of epithelial barrier (e.g. surgery)
• neutrophil depletion (e.g. chemotherapy)
• genetic disorders (e.g. defective phagocyte function seen in chronic granulomatous disorder)

Question 22

aspergillus risk factor

Answer 22

• neutrophil depletion (e.g. chemotherapy)
• genetic disorders (e.g. defective phagocyte function seen in chronic granulomatous disorder)
• high dose corticosteroids (e.g. organ transplant)

Question 23

cryptococcus risk factor

Answer 23

• impaired cell-mediated immunity
• corticosteroids

Question 24

current challenges in the field

Answer 24

• mostly due to opportunistic pathogens
• airborne sources of infection
• poor diagnostics
• few antifungal therapies
• resistance to current (and potentially novel) antifungals
• no antifungal vaccines

Question 25

antifungal drugs classes

Answer 25

• triazoles
• echinocandins: canspofungin
• polyenes: amphotericin B
• 5-FC

different classes are used to treat different fungal diseases

Question 26

the rise of antifungal resistance

Answer 26

resistance is the inherited ability of microorganisms to grow at high concentrations of an antibiotic
- intrinsic (primary resistance): organisms that are naturally resistant to a drug
- acquired: resistance is acquired due to exposure to drug

Question 27

what is driving drug resistance

Answer 27

the extensive use of azoles in crop protection and horticulture is driving drug resistance