Fungi: introduction, mycoses and antifungal agents (L3)

• Around 100,000 species of fungi have been described, and 300 species are presently known to be pathogenic to man
• Types of fungi


  • Mushroom
  • Yeasts
  • Moulds
• Fungi


  • Able to grow at low water activity (Aw)
  • Are EUKARYOTES
  • They do not contain chlorophyll
  • Are filamentous structures
  • Produce spores
  • Grow as saprophytes
• Yeast


  Unicellular organisms that reproduce by budding
• Moulds


  Multicellular filamentous organisms, also known as hypha and mycelium, reproduce by spores
• Dimorphic fungi


  Fungi that occur in both yeast and mycelial forms
• Mycosis


  A disease caused by a fungus
• Mycotic diseases are generally not communicable
• Types of fungal diseases

  • Allergies
  • Mycotoxicoses
  • Mycoses
• Allergies


  Resulting from hypersensitivity to fungal antigens (e.g. inhaled fungal spores)
• Mycotoxicoses


  Resulting from ingestion of fungal toxins in contaminated food or poisonous mushrooms
• Mycoses


  Resulting from ingestion invasion of living tissue by a fungus
• Classification of mycoses


  • Systemic Infection (Deep)
  • Superficial Infection
• Systemic Infection (Deep)


  Affecting tissues or organs, e.g. histoplasmosis which is a disease that affects primarily the lungs
• Superficial Infection


  Affecting skin, nails, scalp or mucous membranes, including dermatomycoses and candidiasis
• Fungal cell wall


  • Maintain structure
  • Protect against mechanical injury
  • Prevent osmotic lysis
  • Provide passive protection against internalisation of potentially harmful macromolecules
  • Determine final morphology of fungus
  • Composed largely of chitin, a polymer of N-acetylglucosamine
• Moulds


  • Multicellular organisms
  • Reproduce asexually by spore formation or by fragmentation
  • Grow on a wide variety of substrates
  • Used in production of antibiotics and cheeses
  • Aerobic organisms
  • Can be killed by mild heat treatments (but mould spores are more resistant to heat)
• Typical yeast cell


  • Made of a cell wall which contains: nucleus, mitochondrion, storage granules
  • Often forms a bud
  • Parent cell and bud contain vacuoles
  • Once budding has occurred, a bud scar remains on the cell wall
  • Yeasts have 3 membranes: Cell membrane, vacuolar membrane and nuclear membrane
• Fungal reproduction


  • Growth and spread of hyphal filaments
  • Asexual production of spores
  • Simple cell division "Budding"
• Some fungi produce spores as a result of sexual reproduction
• Subcutaneous mycosis


  • Chromoblastomycosis (Fonsecaea pedrosoi)
• Systemic mycosis


  • Blastomycosis (Blastomyces dermatitis)
• Opportunistic mycosis


  • Candidosis/Candidiasis (Candida albicans)
• Targets for antifungal therapy

  • Cell wall
  • Plasma membrane
  • Mitochondria
• Modes of action for antifungal agents

  • Impairment of cell wall synthesis
  • Impairment of fungal cell membrane
  • Inhibit nuclear acid synthesis
  • Inhibit fungal mitosis
• Impairment of cell wall synthesis


  Cyclic lipopeptides act by interfering with fungal cell wall synthesis by inhibition of ß-(1,3) D-glucan synthase, e.g. caspofungin
• Inhibit nuclear acid synthesis

  1. Flucytosine is converted to 5-fluorouracil which inhibits both DNA and RNA synthesis
• Inhibit fungal mitosis


  Griseofulvin binds to intracellular microtubular protein and inhibits fungal mitosis
• Non-specific treatments for dermatophyte infections


  • Whitfield's Ointment (Compound Benzoic Ointment)
  • Castellani's Paint
  • Undecenoate fatty acid
  • Ciclopirox
  • Tolnaftate
• Non-specific treatments for pityriasis versicolor

  • Selenium Sulphide 2.5%
  • Sodium thiosulphate 20%
• Types of mycosis:

  • Superficial
  • Cutaneous
  • Subcutaneous
  • Systemic
  • Opportunistic
• Superficial mycosis

  Pityriasis versicolor (Malassezia furfur)
• Cutaneous

  Tinea pedis/Onychomycosis (Trichophyton rubrum)
• Impairment of fungal cell membrane

  • Polyene macrolide antibiotics
  • Azoles antifingals
  • Terbinafine
• Polyene macrolide antibiotics (amphotericin B and nystatin)

  • Bind to membrane ergosterol in the fungal cell membrane, forming a pore
  • Leakage of ions and macromolecules occur, causing irreversible fungal cell damage
• Azoles anitifingals (imidazole and triazole)

  • Blocks synthesis of ergosterol from lanosterol which inhibits fungal membrane growth
  • Therefore interferes with membrane-bound enzyme systems
  • Triazoles have greater selectivity against fungi than imidazoles
• Terbinafine

  • Selectively inhibits the enzyme squalene peroxidase which inhibits the synthesis of ergosterol
  • Causes accumulation of toxic squalene within fungal cell leading to fungal cell death