4 The fungi Flashcards
Mycology is study of fungi, and infections known as mycoses. 70 000 species, but only 300 pathogenic to animals/ humans
Eukaryotes.
Gain nutrients by releasing enzymes and digest food externally.
What structure of fungal cell membrane and wall
Mannoproteins
Beta-Glucans
Chitin - polysaccharides
Cell membrane - phospholipid bilayer which uses ergosterol, and has beta glucan synthase
What are two major ways of classifying mycoses
Fungal infection become more prominent given rise in immunocompromised patients, transplants, invasive procedures
By growth form -
- Filamentous (moulds) - multinucleate thread-like filaments hyphae which grow by branching. A mass of hyphae is termed a mycellium. Grow extracellularly
- Yeasts - unicellular, round or oval and reproduce by budding. Can survive within neutrophils/ macrophages
( some can show both growth forms during cycle called dimorphic fungi)
Or by type of infection -
- superficial
- deep mycoses
Other forms such as mushrooms can occur
How do filamentous forms replicate and spread
Form hyphae to spread
Asexual reproduction - form sporangia which are sacs containing spores, at end of hyphae.
These rupture and disperse spores to continue life cycle. Spores can be inhaled and cause disease
Spores can also independently divide in certain conditions
How do yeast like forms reproduce and spread
Single cell reproduces by budding. Bud remains attached, and further budding leading to formation of chains known as pseudohyphae
What are three main types of mycoses
Superficial - grows on body surfaces e.g skin, hair, nails, mouth, vagina
Subcutaneous mycoses - nails and deeper layers skin
Systemic/ deep mycoses - can be opportunistic or can infect with normal immunity.
How are three types of mycoses spread
Superficial - person to person or animal- person contact
Subcutaneous - following skin penetration e.g mycetoma
Systemic - usually via respiratory tract or IV lines
Occasionally free-living fungi can cause disease. Occurs indirectly when fungi present in food - e.g aflatoxin carcinogen produced by aspergillus. Or when inhaled spores can cause immune response hypersensitivity pneumonitis (allergic bronchopulmonary aspergillosis)
Candida can be part of normal flora, but only causes problems if immunocompromised or IV lines or diabetes
What are causes of -
- superficial fungal disease (hair, dead skin layer), and which diseases do they cause
- superficial fungal disease
Pityriasis versicolor
Tinea nigra
Piedra
Trichosporon
Malassezia
Exophilia
What are causes of
- cutaneous fungal disease ( epidermis, hair, nails), and what diseases do they cause
- cutaneous fungal disease
Tinea (ringworm
Trichophyton
Microsporum
Epidermophyton
What are causes of -
Systemic fungal disease (deep mycoses) and organism name
Immunocompetent host
Blastomycosis - blastomyces
Coccidiodomycosis - coccidioides
Histoplasmosis - histoplasma
Paracoccioidomycosis - paracoccidioides
What are causes of -
Systemic fungal disease (deep mycoses)
Yeasts/ moulds
Immunocompromised host
Yeasts -
Candida
Cryptococcosis
Moulds (filamentous) - Aspergillosis Pneumocystis Mucormycosis Dimorphic fungi - Blastomycosis/ Coccidioides/ Histoplasma/ Penicillium
What is structure of fungal plasma membrane
Below cell wall is cell membrane called plasmalemma. Unlike humans where dominant sterol is cholesterol, fungal membrane rich in ergosterol. Compounds that selectively bind to ergosterol can be used as anti-fungal agents
What is mechanism of action, and example of antifungal
Echinocandins
Polyenes
Echinocandins - inhibit beta-(1,3)-D-glucan synthase, preventing glucan synthesis in fungal cell wall. Anidulafungin, capsofungin, micafungin
Polyenes - bind to ergosterol and disrupt cell membrane. Nystatin, amphotericin B
What is mechanism of action, and example of antifungal
Allyamines
Pyrimidines
-Allyamines - inhibit ergosterol synthesis. Terbinafine
Pyrimidines - Flucytosine is deaminated 5-fluorouracil which inhibits nucelic acid synthesis. Resistance emerges quickly when given as single agent
What is mechanism of action, and example of antifungal
Heterocyclic benzofuran
Topical antifungals
Heterocyclic benzofuran - interferes with hyphae mitosis
Topical - ciclopirox - inhibit uptake of key nutrients, tolnaftate - distorts hyphae and prevent growht
What is mechanism of action of these antifungals:
Griseofulvin
inhibit nucleic acid synthesis
antimitotic activity inhibiting microtubule assembly
What is mechanism of action, and example of antifungal
Azoles
Azoles - inhibit C14-demethylase, important for ergosterol synthesis. Miconazole, ketoconazole, itraconazole
Some fungi can exist in both yeast and mould forms, depending on environemntal conditions. What are examples of this?
Coccidioides
Histoplasma
Fungi can utilise amino acids absorbed via cell wlal, but larger proteins must first be broken down by extracellular enzymes.
What are these methods of fungal energy production?
Biotrophs
Saprotrophs
Chemoheterotrophic
Photoheterotrophic
Biotrophs - nutrients from living host
Saprotrophs - nutrients from dead plants/ animals
Chemoheterotrophic - organic carbon in environment
Photoheterotrophic - use light for energy, cannot use carbon dioxide as sole carbon source
Fungi life cycle can either be asexual or sexual.
Describe asexual life cycle
Mitosis -
- Mycelium undergoes mitosis to produce spores
- Spores germinate
- Produce further mycellium
Fragmentation -
- ends of hyphae detach by fission/ budding or break down, to produce fragments (arthrospores) that can develop into new individuals.
Offspring are genetically similar to parents
Fungi life cycle can either be asexual or sexual.
Describe sexual life cycle
Plasmogamy - haploid cells form two different mycelia fuse to form heterokaryotic cell with two or more nuclie
Heterkaryotic stage
Karyogamy - nuclei fuse to form diploid zygote
Zygote stage
Meiosis - haploid spores formed
Spores germinate - new mycellium formed
what is structure of fungal spore?
Outer exosporium cell wall - resistant to heat/ cold/ dessication/ pH changes
Inner core contains glycogens/ lipids for nourishment. Although reduced metabolism when dormant
Spores capable of germinating to produce new hyphae when conditions improve
Spores provide challenge to hospital infection prevention/ control as require specific methods of sterilisation to ensure they are effectively killed
HIV patient present confusion/ photophobia. Does not takes ART. CD4 10. India ink positive.
Which fungal kingdom does likely pathogen belong to?
Asomycota Basidiomycota Chytridiomycota Glomeromycota Neocallimastigomycota
Basidiomycota - cryptococcus belongs to this
Mouth swab shows oral candida
Why can it be detected so quickly?
Produces germ tube within 2-4 hours
Germ tube is an early hyphae outgrowth
HIV patient with two week history of fever, lymphadenopathy, hepatosplenomegaly. Born in Thailand, moved to UK recently
CD4 80
Blood culture - yeast
What is most likely organism?
Blastomyces dermatitidis Candida albicans Cryptococcus gattii Histoplasma penicillum Talaromyces marneffei (formerly penicillosis)
Talaromyces marneffei - Talaromycosis
CD4 low, so risk of yeast infection.
Histoplasma/ blastomycoses restricted to North America. Cryptococcus more likely to cause meningitis. Candida would rarely cause hepatosplenomegaly
Talarymyces seen in SEA
What is treatment of talaromycosis? (penicilliosis)
Amphotericin B IV 2 weeks then
itraconazole for 10 weeks
What are dimorphic fungi?
What are examples?
These are fungal infections of the body caused by fungal pathogens which can overcome the physiological and cellular defences of the normal human host by changing their morphological form. Can exist as mould and yeast
They are geographically restricted and the primary site of infection is usually pulmonary, following the inhalation of conidia
Blastomycosis Coccidiomycosis Paracoccidiomycosis Histoplasmosis Talaromycosis Sporotrichosis
What is geographical spread of these dimorphic fungi?
Blastomycosis Coccidiomycosis Paracoccidiomycosis Histoplasmosis Talaromycosis
Blastomycosis - NA
Coccidiomycosis - NA
Paracoccidiomycosis - SA
Histoplasmosis - NA/ SA/ Africa
Talaromycosis - SEA
Which anti-fungals act at these sites?
Act on nucleus/ protein synthesis
Act on cell wall
Act on cell membrane
Act on nucleus/ protein synthesis -
griseofulvin
flucytosine
Act on cell wall -
echinocandins
Act on cell membrane -
azoles
polyenes
allyamines
