Fungi

Fungi

Fungi

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Types of Microorganisms

  • Bacteria - unicellular - bacteriology
  • Fungi: yeast and moulds - unicellular or multicellular - mycology
  • Protozoa - unicellular - protozoology
  • Helminths - multicellular
  • Viruses - non-cellular - virology
  • Prions - non-cellular (e.g. mad cow disease)
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Simple Classification

  • Microscopic
    • Unicellular (yeast)
    • Multicellular (moulds)
  • Macroscopic
    • Toadstools
    • Mushrooms
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Fungi and Mycology

  • 90,000 fungal species - only about 50 cause human diseases - mycoses 
  • Eukaryotic
  • Spore-bearing
  • Absorptive nutrition
  • No chlorophyll
  • Reproduce sexually and asexually 
  • Cell wall made of chitin (polysaccharide)
  • Body or vegetative structure is thallus
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Fungi

  • Saprophytes
    • Live on dead plant and animal material
  • Parasites
    • Live on/in living material
  • Fungal metabolism
    • Aerobic (e.g. generate ATP from glycolysis)
    • Facultative anaerobes - fermentation (make ethyl alcohol from glucose)
    • Obligate anaerobes (rumen of cattle)
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Examples of Fungi - Yeasts

  • Saccharomyces cerevisiae (mean generation time 2 hours)
  • Candida albicans
  • Cytoplasmic membrane: Ergosterol - unique sterol in the fungal membrane
  • Chitin - polymer of N-acetyl glucosamine - may make up 80% of cell wall
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Chitin

  • A natural polymer of N-acetyl glucosamine (polysaccharide)
  • Absent of mammalian cells: target for antifungal chemotherapy
  • Treatment: caspfungin (IV 70mg daily for 1 day then 50mg once daily - adult up to 81kg)

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Ergosterol

  • Unique sterol in fungal cell membrane
  • Synthesis of ergosterol for incorporation into the plasma membrane
  • Makes the plasma membrane sensitive to antimicrobial agents which either block the synthesis of ergosterol or prevent its incorporation into the membrane or bind to it, e.g. azoles, polyene, antifungals
  • Treatment: Azole antifungals/amphotericin

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Reproduction

  • Sexual and asexual

Yeast: Candida spp.

  • Dimorphic
  • Can change from yeast form to mycelial, depending on environmental factors
    • Nutrients
    • Carbon dioxide
    • Temperature
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Mould

  • Long branched thread-like filaments of cells (hyphae)
  • Hyphae form mycelium
  • Hyphae can be continuous or crossed walles septa
  • Distinct spore structure (identification)
  • One single spore produces one new colony (enumeration)
  • Fungal diseases are named mycoses

Fungal Diseases

  • Local - skin
  • Systemic - candidiasis
  • Fungal spores
    • Inhaled
    • Cut or wound
  • Damaged to host cells
    • Can be related to the release of enzymes (toxin)
    • Direct physical damage
  • Toxins (mycotoxins)
    • Intoxication (ingestion)
    • Infection
    • Allergies
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Mycoses

  • Dermatophytes
    • Three fungal species associated with skin infections - Epidermophyton, Microsporum, Trichophyton
  • Ringworm - Tinea - can affect most skin sites
    • Tinea pedis is athletes foot
    • Tinea cruris is jock itch
    • Tinea capitis is ringworm of the scalp
    • Tinea corporis is ringworm of the body and nails
  • Treatment: itraconazole (100mg daily for 30 days)
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Candidiasis

  • Candida albicans
  • Yeast colonies
  • Diseases: Candidiasis
  • Sabouraud glucose, agar, 25 degrees
  • Most common cause of opportunistic mycoses worldwide
  • Physiological: Pregnancy, age (elderly and infancy)
  • Trauma: infection, burn would
  • Haemtological: cellular immunodeficiency
  • Endocrinological: Diabetes mellitus
  • Iatrogenic: Chemotherapeutics, corticosteroids, antibiotics, catheters, surgery
  • Others: intravenous drug addiction, malnutrition
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Candidiasis

  • Candida albicans
  • Strict aerobe
  • Dimorphic
  • Normal microflora (skin, mucousal surfaces)
  • Oropharyngeal Candidiasis - oral thrush
  • Nappy (diaper) Candidiasis
  • Candidal vaginitis
  • Bone marrow transplant
  • Blood stream infection common in hospitals 
  • HIV
  • Treatment: Clotrimazole (vaginitis) cream/pessaries - superficial/deep/recurrent
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Aspergillosis

  • Entry - usually respiratory tract
  • Pulmonary aspergillosis
  • May cause an immediate allergic response
  • Invasive asperglillosis - organism can spread from the lung to many organs - most commonly occurs in the severely immunocompromised patients with neutropenia, usually leukaemia patients or those receiving chemotherapy or corticosteroids
  • Treatments: voriconazole (IV 6mg/kg 12 hours for 2 doses)
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Antifungal Chemotherapy

  • Fungi are eukaryotes therefore treatment is more difficult
  • > similarity to human
  • Drugs tend to be more toxic
  • Repeated applications
  • Lengthy treatments
  • Antifungal drug targets:
    • Proteins (enzymes): involved in fungal membrane synthesis (ergosterol), enzyme chitin synthase (cell wall), beta-1,3D-glucan synthase (cell wall)
    • Membranes - drugs that interact with membrane sterols
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Amphotericin B

  • Natural antifungal (1955): Streptococcus nodosus
  • Very broad spectrum of activity (yeasts and moulds)
  • Toxicity is a problem
    • Cardiovascular
    • Renal
    • Hepatic
  • Liposomal preparation
    • Fungizone (IV 1mg/20min; 250mg/kg daily)
    • AmBisome - liposomal (IV, 1mg/10min, 1mg/kg daily)
  • Systemic treatment
  • Binds to sterols primarily fungal cell membrane ergosterol
  • Binding disrupts osmotic integrity of fungal membrane - leakage of intracellular potassium, magnesium, sugars and metabolites
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Itraconazole

  • Triazole antifungal (1984) - synthetic
  • Active against moulds
  • Inhibits cytochrome P450 14alpha-demethylase (P45014DM)
  • Enzyme required in the sterol biosynthesis pathway: ianosterol --> ergosterol
  • Side effects - caution with patients with high risk of heart failure
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