Fungi, Fungal + Anti-fungal infections

Question 1

Key structural differences between fungi + human cells

Answer 1

• Rigid wall = made from Chitan (or glucan + mannan)
• cytoplasmic membrane contains Ergosterol
  But both eukaryotic cells

Question 2

Examples of fungi

Answer 2

Moulds, yeast + mushrooms

• penicilium
• aspergillus
• saccharomyces
• candida

Question 3

What are fungi an example of

Answer 3

Heterotrophic (saprotrophy, symbiosis + parasitism)

Question 4

How many phyla do they have?

Answer 4

4

Question 5

Name the phyla

Answer 5

Ascomycota, basidiomycota, zygomycota, chytridiomycota

Question 6

2 variable fungal morphologies

Answer 6

Hyphae - network of filaments e.g. moulds + mushrooms

Single celled budding organisms e.g. yeasts

Question 7

What fungi can convert from the fungal morphologies

Answer 7

Dimorphic fungi can convert between hyphae + yeast depending on temperature

Question 8

Sporulation

Answer 8

spores allow fungi to spread, maintain genetic diversity + survive adverse conditions
Spores are airborne - which contribute to allergies + specific, life-threatening conditions (histoplasmosis/coccidiomycosis)

Question 9

What causes fungal infections?

Answer 9

• overgrowth of natural flora
• inhalation of fungal spores
• traumatic implantation
• primary/secondary to other conditions (HIV/immunocompromised)

Question 10

What are the fungal pathogenicity factors?

Answer 10

• adhesion to host cells
• capsules to prevent phagocytosis
• secrete various biochemical factors to help tissue invasion/spread + suppress immune response

Question 11

What are infections classified by?

Answer 11

Location + opportunism

Question 12

5 classifications

Answer 12

Superficial
Subcutaneous
Cutaneous
Systemic
Opportunistic

Question 13

Example of superficial

Answer 13

Piedras

Question 14

Example of cutaneous

Answer 14

Tineas

Question 15

Example of subcutaneous

Answer 15

Mycetoma, chromablastomycosis, sporotrichosis

Question 16

Example of systemic

Answer 16

Blastomycosis
Cryptococcal meningitis
Histoplasmosis
Coccidiomycosis

Question 17

Example of opportunistic

Answer 17

Candidosis, aspergillosis

Question 18

What do opportunistic pathogens cause?

Answer 18

Localised mucosal/ systemic infections

Question 19

Who are susceptible to opportunistic fungal infections?

Answer 19

Immunocompromised patients (aid/hiv, elderly, infants, transplant patients - as immune system is suppressed)

Question 20

Examples of poisoning - fungal infections

Answer 20

Ergot in wheat
Aflatoxin in peanuts
Mushrooms/toadstools

Question 21

What are poisoning - fungal toxins called?

Answer 21

Mycotoxins

Question 22

What is mycoses?

Answer 22

Fungal infection

Question 23

Superficial mycoses

Answer 23

Harmless - cosmetic ‘blemishes’
Cause minimal destructive disease
Rarely induces an immune response

Question 24

Treatment for Superficial mycoses

Answer 24

Selenium-based shampoo
Nizoral body wash
Topical antifungals
Good personal hygiene

Question 25

Cutaneous mycoses

Answer 25

Dermatophyte fungi that eat keratin protein in hair, nails and skin Cause chronic conditions cause Tineas Can start inflammatory reactions from host Contagious Respond well to topical agents Systemic therapy required for extensive infection

Question 26

Name the different Tineas

Answer 26

Tinea capitis - infection of hair + scalp Tinea corporis - ringworm of trunk, legs + arms Tinea pedis athletes foot Tinea cruris - jock itch (genital region) Tinea urguium - onychomycosis, nail infection

Question 27

Subcutaneous mycoses

Answer 27

Infection arises after fungi is introduced by trauma, small wounds, splinters, thorns, Infects skin + underlying tissues May require amputation or surgical excision

Question 28

Systemic mycoses

Answer 28

Opportunistic pathogens e.g. immunocompromised patients Caused by spore inhalation (lungs) e.g. Histoplasmosis, coccidioidosis, aspergillosis, blastomycosis or spread from mucosal infections e.g. Candidiosis Lung: pneumonia or flu-like symptoms, followed by spread to other organs, systemic infection Rapid diagnosis + aggressive therapy Caused by dimorphic fungi

Question 29

Outline the opportunistic mycoses

Answer 29

Candida albicans Aspergillus fumigatus Cryptococcus neoformans Pneumocystis spp.

Question 30

Candida Albicans

Answer 30

Component of mucosal + cutaneous microflora Oral thrush + antibiotic use/immunocompromised Vaginal thrush (common in women) Candidiosis (common in diabetes, cancer, HIV, burns patients) Systemic infection linked with immunocompromised patients with catheters, burns or post surgery Dimorphic - linked to pathogenicity

Question 31

Aspergillus fumigatus

Answer 31

Cause of pulmonary aspergillosis (asthma, cystic fibrosis) Found in wet soil, damp surfaces Caused by spore inhalation (route of infection) Causes allergic reactions in asthma + CF patients Release toxins, phospholipases, haemolysins + facilitate spread to other tissues

Question 32

Pneumocystis spp.

Answer 32

Environmental fungus Inhaled spores affect patients with aids + premature infants Pneumonia

Question 33

Cryptococcus neoformans

Answer 33

``` Found in soil contaminated with bird droppings Cause by spore inhalation Affects immunocompromised patients Cause of meningitis in AIDS patients Surrounded by a capsule phagocytosed by macrophages Survives + multiplies within macrophage ```

Question 34

Classes of antifungals used to treat fungal infections

Answer 34

Polyenes Azoles Nucleoside Echinocandins

Question 35

What do Azoles target?

Answer 35

Ergosterol synthesis - bind to fungal p450 enzyme - cell membrane stability disrupted

Question 36

What do Polyenes target?

Answer 36

Cell membrane - bind to ergosterol in cell membrane - causes cell leakage - renal toxicity (side effect)

Question 37

What do Nucleoside derivatives target?

Answer 37

DNA/RNA synthesis | - selective uptake / metabolic activation in fungal cell

Question 38

What do Echinocandins target?

Answer 38

Cell wall synthesis - blocks B1-3 glucan polymer synthesis - destabilises cell wall

Question 39

Polyene examples

Answer 39

Amphotericin B - fungicidal They can damage fungi better than mammalian cells as they prefer ergosterol-containing membranes Low dose = leakage of essential ions from cytosol High dose = cell destruction Intravenous injection Poor selectivity; lipid complex or liposome may help

Question 40

Azole examples

Answer 40

Imidazoles + Triazoles - largest group of antifungals (fungistatic) Inhibit 14a - demethylation of 24 methyledihyydrolanosterol (ergosterol precursor) Leads to - depletion of ergosterol - accumulation of 14a-methylated sterols resulting in growth arrest Reaction dependent upon cytochrome p450; azoles bind haem component of cytochrome p450 Not entirely selective - interferes with mammalian sterol metabolism (testosterone)

Question 41

Nucleoside examples

Answer 41

Flucytosine | Used orally to treat systemic infections

Question 42

Mode of action of nucleosides

Answer 42

Taken up by cytosine permease Rapidly deaminated to 5-fluorouracil (gives fungal selectivity) Converted to 5-fluorouridylic acid monophosphate (FUMP, inhibits RNA function) or 5-fluorodeoxyuridine monophosphate (inhibits DNA synthesis)

Question 43

Other treatment for fungal infections

Answer 43

Grisans Allylamines Morpholines

Question 44

Resistance in antifungals

Answer 44

Exposure to fungal pathogens to antifungals

Question 45

Enchinocandins examples

Answer 45

Capsofungin Micafungin Anidulafungin

Question 46

Resistance mechanism to polyenes

Answer 46

Lower production of membrane sterols Altered sterols bind drug with lower affinity Reorientation/masking existing ergosterol

Question 47

Resistance mechanism to Nucleosides

Answer 47

Decreased uptake Loss of enzymatic activity Resistance develops rapidly (with other antifungals it is fine)

Question 48

Resistance mechanism to enchinocandins

Answer 48

Resistance to glucan synthesis

Question 49

Resistance mechanism to azoles

Answer 49

Increase target enzyme by gene amplification / upregulation of encoding gene Mutations in lanosterol demethylase enzyme Active efflux

Question 50

Other resistant mechanism

Answer 50

Formation of biofilms | - poor pentration of antifungals into biofilms + efflux pumps are upregulated