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Microbiology BIO-5015B > Lecture 22: Fungal Toxins and Infections > Flashcards

Lecture 22: Fungal Toxins and Infections Flashcards

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1
Q

What are different types of fungal poisoning?

A
  1. Mycetism - poisoning by mushrooms

2. Mycotoxicoses - poisoning by fungi

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2
Q

What is mycetism?

A
  1. Results from ingestion of mushroom that
    contain “performed” toxic metabolites
  2. E.g:
    a. Ibotenic acid from amanita muscaria
    b. Amatoxins from amanita phalloides
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3
Q

What are the toxins of amanita muscaria?

A
  1. Produces “ibotenic acid”.
    a. an unstable thermolabile amino acid
    which can be decarboxylated to
    “muscimol”
    b. glutamate receptor agonist
    (activator)
  2. Muscimol:
    a. agonist of gamma-aminobutyric acid
    (GABA) receptors
    b. Insecticidal properties
  3. BOTH affect neurotransmission
  4. Symptoms similar to alcohol:
    a. staggering
    b. delirious
    c. loses consciousness
  5. death in 1% of cases from respiratory
    failure
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4
Q

What are amatoxins?

A
  1. at least 9 known amatoxins
  2. among deadliest poisons in nature
  3. occurs in fungal genera:
    a. amanita (most poisonous)
    b. galerina
    c. lepiota
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5
Q

What is alpha-amanitin?

A
  1. potent inhibitor or RNA polymerase 2
  2. it causes kidney failure, liver failure,
    coma and death
  3. One mushroom or less may be fatal
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6
Q

What are phallotoxins?

A
  1. at least 7 known
  2. Occur in fungal genera:
    a. amanita
    b. galerina
    c. lepiota
  3. They are structurally related to
    amatoxins
  4. “Phalloidin” - binds to F-actin,
    preventing depolymerisation and
    highly toxic to liver cells
  5. Phallotoxins are only poorly absorbed
    by the gut and thought to not
    contribute significantly to poisoning
    by death cap
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7
Q

How is mushroom poisoning treated?

A
  1. Needs to be quick
  2. Evacuation of gastrointestinal tract
    performed by inducing vomiting,
    stomach lavage, or enemas
  3. carbon may be given to absorb toxins
  4. kidney and liver monitored
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8
Q

What is mycotoxicoses?

A 
1. Intoxication through ingestion of fungi 
   producing toxins ("mycotoxins") 
   growing on foodstuffs
2. Associated with specific food
3. Seasonal, non-transmissible, 
    unresponsive to drug and antibiotic 
    treatment
4. >100 species of filamentous fungi are 
    known to produce mycotoxins
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9
Q

What are Ergot alkaloids?

A
  1. Ergot is a mixture of:
    a. alkaloids produced by species of
    genus Claviceps (especially C.
    purpurea)
    b. /\ grows on rye and related species
  2. Kernels infested with fungus develop
    dark curved pegs called “sclerotia”
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10
Q

What are different ergot alkaloids?

A
  1. D-lysergic acid
  2. Ergine
  3. Ergonovine
  4. LSD-25
  5. Pibocin
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11
Q

What are the effects of alkaloids?

A
  1. Vasoconstriction + uterus contraction
    (myotic abortion)
  2. CNS: reduce activity of vasomotor centre
    whilst stimulating sympathetic regions of
    mid brain (especially hypothalamus)
  3. Natural role: deter animal grazing
  4. Important for starting material for drug
    production - many used for human
    treatment (migraine and Parkinson’s
    disease)
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12
Q

What are Aflatoxins?

A
  1. Produced by Asperigillus flavus
  2. Most dangerous mycotoxins, mainly
    affects animals
  3. Responsible for killing 100,000 turkeys in
    a few months within a 100 mile radius of
    London in 1960
  4. from contaminated foodstuffs. E.g.,
    a. peanuts
    b. cottonseed
    c. coconuts
    d. corn
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13
Q

What are the four principle aflatoxins and what are they produced by?

A
  1. B1
  2. B2
  3. G1
  4. G2

Prod. by a range of fungi:

a. Aspergillus flavus
b. A. parasiticus
c. A. ostianus
d. et al

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14
Q

What are the effects of aflatoxins?

A
  1. Children more sensitive than adults -
    may affect development
  2. Most characteristic effect:
    a. Liver damage
    b. Necrosis
    c. Cirrhosis
    d. Carcinoma
  3. Aflatoxins intercalate into DNA = DNA
    damage (“alkylation”) + chronic exposure
    increases cancer risk, especially in liver
    and gall bladder
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15
Q

What is medical mycology?

A 
1. Study of fungi capable of causing  
   disease in animals and humans
2. ~ 400 species are agents 
3. Natural disease environment for most 
    fungi is soil, when they live as 
    saprophytes
4. Facultative parasites, become     
    parasites when opportunity arises
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16
Q

When and by who isolated the fungus from ringworm

A
  1. 1841

2. David Gruby

17
Q

What is meant by dimorphism in fungi?

A
  1. Single cells (yeast) or mycelial form
  2. Mycelial form outside of host
  3. Conditions inside host cause conversion
    of mycelium:
    a. Elevated temperatures
    b. High CO2 and low O2
    c. Levels of nutrients
18
Q

How does fungal superficial infection take place?

A 
1. Colonisation of superficial layers of 
   tissue, e.g., 
   a. hair
   b. skin
2. E.g., Piedraia hortae - tropical 
    disorder causing dark nodules on hair 
    shaft
3. Cause little damage, and minor 
    importance
19
Q

What is meant by cutaneous infection?

A
  1. Fungi that cause cutaneous damage are
    called - “dermatophytes”
  2. Colonisation of hair, nails, skin
  3. Inflammatory response can be intense at
    site of infection
20
Q

What are examples of tinea infections (types of cutaneous infections)

A
  1. Tinea corporis (ringworm)
    a. red, raised lesions
    b. itchy
  2. Tinea cruris (jock itch)
  3. Tinea pedis (athletes foot)
    a. most common
    b. found in toe webbing
    c. Most often caused by: Trichophyton
    rubrum, T. mentagrophytes, and
    Epidermophytom floccosum
21
Q

What are subcutaneous infections?

A
  1. Can access subcutaneous tissue via
    wounds; typically scratches from thorns
  2. Prevalent in rural and tropical regions
  3. Localised infections
  4. Form abscesses called mycetomas
  5. E.g., Sporothrix schenckii - occurs in
    farmers and gardeners
22
Q

What is systemic infection?

A
  1. Spreading of fungus from one internal
    organ to another
  2. Often systemic mycosis originates in
    lungs via “inhalation of spores” -
    infection of brain quickly leads to death
23
Q

How are systemic infections diagnosed?

A 
1. Based on "clinical observation" and 
   "laboratory investigation"
2. Laboratory investigation relies on:
   a. microscopic examination of causal 
       agent
   b. Isolation of fungus by culture
   c. Diagnostic serological or PCR tests
3. Specimens taken from as many sites     
    as possible. E.g., 
   a. urine
   b. sputum
4. Lung biopsy may be performed for 
    pulmonary mycotic infections
24
Q

Explain the in vitro culturing of fungi

A
  1. Mostly easy to grow pathogenic fungi
  2. Agar medium composed of
    a. Sabouraud’s glucose agar
    b. 4% malt extract agar
  3. For more pathogenic dimorphic fungi;
    “brain-heart infusion agar” and “blood
    agar” are effective for yeast growth
    phase
25
Q

What is meant by serology diagnosis

A 
1. Serology tests for detection of fungal 
   antigens or specific antibodies to 
   pathogenic fungi
2. types of test include:
   a. Immunodiffusion
   b. Whole cell agglutination
   c. Enzyme-linked immunosorbent      
       assay (ELISA)
3. Effectiveness of each technique 
    depends on disease
26
Q

What are molecular methods for diagnosis?

A
  1. PCR currently being developed for diagnosis

2. Sensitivity of PCR opens door to false positives

27
Q

What are 4 important fungal diseases?

A
  1. Aspergillus fumigatus - causes aspergillosis
  2. Aspergilloma - causes aspergilloma
  3. Candidiasis
  4. Cryptococcus
28
Q

What is aspergillosis?

A
  1. Causes aspergillosis
  2. Type: Aspergillus fumigatus
  3. Sometimes occurs in farmers and people
    handling decaying organic matter
  4. Leukaemia and immunosuppressive
    disorder patients at risk
  5. Spores inhaled germinate, hyphae
    penetrate tissue and invade blood
    vessels = thrombosis occurring
  6. A. fumigatus can also cause myotic
    abortion and eye ulcers when
    introduced via wound
29
Q

What is aspergilloma?

A
  1. Referred to as “fungus ball”
  2. Commonly caused by A. fumigatus
  3. Occupies previous existing cavities in
    lung, particularly old tuberculosis
    lesion, forming compact ball of mycelia
  4. Resulting aspergilloma becomes
    surrounded by dense fibrous wall.
  5. Balls are solitary and vary in size
    (generally less than 8cm)
  6. Few symptoms, just moderate cough
  7. However, haemorrhage may occur if
    infection reaches blood vessel -
    Requires “surgical removal”
30
Q

What is candidiasis?

A
  1. “Candida albicans” -predominantly form
    of yeast like cells, capable of dimorphism
  2. Opportunistic, living as saprotroph in
    healthy host
  3. Primarily disease of mucous membrane,
    where soft, grey/white lesions form
  4. Lesions contain mycelium of fungus,
    lying over red oozing mucosa
  5. Systemic infection is rate, if it does
    reach the blood stream though, can
    spread to kidneys, spleen, bone,
    brain, and lungs
  6. Death is very rare
  7. Can occur in other mammals and birds
31
Q

What is Cryptococcus?

A
  1. “Cryptococcus neoformans”
  2. A basidiomycete, having a yeast
    growth form
  3. Found in pigeon roots and nests.
  4. Outbreaks have occurred among
    workers demolishing old buildings
  5. Fundus disseminates the lungs and
    affects the “meninges” - “Crytococcal
    meningitis”
  6. Meningitis occurs most frequently in immuno-compromised patients:
    a. Hodgkin’s disease
    b. AIDS
32
Q

How are fungal infections treated?

A
  1. Often difficult, since both host and
    parasite is eukaryotic
  2. Administration of antifungal antibiotic -
    however there is very few antimycotic
    compounds which can be used in human
    treatment
33
Q

What is “polyene macrolide”

A 
1. Antibiotics produced by Streptomyces 
   spp and include:
   a. amphotericin B
   b. nystatin
   c. pimaricin
2. Common large ring structure
3. Bind specifically to sterol in fungal 
    membrane (ergosterol)
   a. increase permeability 
   b. leakage of cellular constituents   
   c. lysis
   d. death
34
Q

What is amphotericin B?

A 
1. Administered intravenously in a bile 
   salt suspension
2. active agonist of most fungi
3. Treats systemic infection and sever 
    superficial mycosis
4. At low concentrations, antibiotic can 
    also boost immune function
5. Toxic to kidneys at higher 
    concentrations
35
Q

What is nystatin?

A
  1. Too toxic for administration intravenously
  2. cannot be absorbed by digestive tract
  3. therefore used (alongside with pimericin)
    to treat superficial infections such as
    thrush
36
Q

What are the newer antifungal drugs?

A 
1. Imidazole's and triazole's are most 
    effective
   a. broad spectrum, and effect    
       ergosterol in plasma membrane
2. E.g., Ketoconazole can be absorbed    
    through gastrointestinal tract,     
    inhibiting synthesis of ergosterol.     
    NON-TOXIC TO HUMAN CELLS

Microbiology BIO-5015B (30 decks)

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