Fungi
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- Created by: amazingemilyjones
- Created on: 14-04-19 20:43
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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