Fungi Flashcards
Increasing in complexity, it goes viruses, then bacteria, then fungi, then parasites
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Fungi are eukaryotes! They have nucleus, organelles, plasma membrane, CELL WALL, sometimes a capsule!!!!!! and 80s ribosomes.
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The Fungal Cell Wall
- No peptidoglycan!!
- 10% protein
- 90% polysaccharides( glucans, chitins, mannans, galactans)
The Fungal Cell Membrane
- phospholipid bilayer
- Sterol = ergosterol
Funal Nutrition
Feed by absorption! - Many are environmental saprophytes - Relevance: Nutritionally versatile DESTRUCTIVE
What does saprophytes mean?
degrade organic debris into usable nutrients
Two different fungal forms?
Inbetween?
yeasts and molds
DIMORPHIC FORMS.
How do yeast divide?
budding or fission
Word for spore?
Conidium
Growth of molds?
polarized growth from a conidium forms hyphae (filaments)
Grows to create a “germ tube”
Hydrolytic enzymes are on the very tips of hyphae!
Septa divide the hypha into compartments. Septate vs Non-Septate is used diagnostically!
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What is the relevance of molds?
- Invasive behavior
- Diagnostic clues (hyphae, segmented, etc).
Dimorphic Fungi are capable of what?
Examples?
Relevance?
Capable of Switching forms
Examples: environment (moulds); tissue (yeast - or some other non-hyphal form)
Relevance: Virulence factor
Why does a mold switch to yeast in tissue?
stress response!
Fungi can switch forms to avoid the immune system (dimorphic).
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Asexual reproduction of fungi results in what?
Conidia (spores)
Relevance:
- spore forming structures can be used diagnostically (look at pics)
- Unavoidable!!! Fungal spores comprise the majority of the viable airborne biomass (aka if you get sick from them it is probably due to immunosuppression)
Asexual reproduction is basically mitosis.
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Fungi are threats to human when….
1) Food Contaminants:
- crop destruction
- aflatoxin (potent) - works on food
2) Infection…
- 1.5 million species but only 150 cause human disease and only a few are common human pathogens
Most fungi are mesophilic and don’t like 37 degrees celsius!
However!!! as many people die from the top 10 invasive fungal diseases as from Tb or Malaria
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Two aflatoxins?
Aspergillus flavus
Aspergillus parasiticus
Sources of fungal infection?
- Environment (Inhalation/skin wounds)
- Human microbiota (the mycobiome)
**antibiotics can also cause fungi to overgrow because all more space for them even though the antibiotics don’t necessary kill their “good” fungi
Virulence of Fungi?
- Adherence
- Growth at 37 degrees
- Invasive if they are hyphal pathogens (they ignore anatomical barriers)
- Tissue damage (degradative enzymes)
- Host evasion (avoid recognition or escape phagocytic killing) - comes with dimorphism
Opportunistic Fungi
- disease occurs when?
- transmission?
Rarely cause disease in a healthy host!! Disease occurs when a person’s natural defenses are weakened!
Transmission (from the environment, from the normal human microbiota, or from person to person (which is rare))
Example of opportunistic fungi that is environmentally acquired?
Dermatophytes! athlete’s foot
Weakened defense - breaks in part of the skin (skin is innate)
They live in the surface of food and they have a virulence factor that degrades keratin
Example of opportunistic fungi that is endogenously acquired (human microbiota)
Candida albicans - biofilm
- dimorphic
- people have a weakened skin barrier
- forms a ECM that encases them in a polysaccharide matrix - little bits break off and seed the bloodstream!!
- Big problem in hospitals
Three ways that biofilms form bacteria or fungi mess with immune system?
1) matrix prevents immune system from breaking through
2) prevents antibiotics from reaching organism
3) constantly seeding the bloodstream
Ex. Candida albicans biofilms - fungi
Ex of opportunistic fungi - person to person transmittion
Pneumocytsis jirovecci
- Obligate resident of the human lung!
- PtP transmission normally restricted by the immune system
- 1980’s Aids epidemic and it was the life threatening disease that patients got.
- causes pneumocystis pneumonia (PCP)
Most common opportunistic infections in AIDS? Caused by what organism?
Pneumocystis pneumonia (PCP) Pneumocystis jirovecci fungi
Was an AIDS defining illness in the 80s
Didn’t even know it existed until immunosuppression in AIDS patients revealed it in the 80s.
We have had a general increase in mycoses form the 60’s…
- more aggressive cancer therapies
- more invasive procedures
- increased use of antibiotics
- increased longevity (older people get higher infections)
- the AIDS pandemic
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sometimes the weird fungal infection can be a sign of the cancer itself in the bone marrow (backwards of this card)
Primary fungal pathogens are different than opportunistic pathogens because they are capable of what..
infecting a healthy person!!! Disease is worse in immunocompromised patients.
Transmission of primary fungal pathogens?
From the environment
Histoplasmosis is a dimorphic pathogen (fungi). We inhale/eat the spores and then they change to yeast. The yeast form is resistant to macrophage killing and it causes granulomas. Ohio is endemic for it.
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How to prepare fungi specimens? (2)
1) KOH! (tissue dissolves but fungi elements preserved - protected by its cell wall)
2) Silver stains
* *They are often large enough to be visible
Can also culture fungi but it tends to grow slower than bacteria. Selective medium is used to suppress bacterial growth!
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Lab testing for fungi
1) antigen testing - cell wall components (blood, urine)
2) serology
3) NAAT
4) Maldi-TOF - mass spec emerging - slower for fungi than for bac
Innate immunity is the first line of defense against fungal infections.
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What are PAMPs of fungi?
Beta-glucan
What are the PRRs for fungi? - on phagocytic cells
Dectin-1
Phagocytic cells?
macrophages, neutrophils, dendritic cells
Inhaled dorman spores = low risk and quietly cleared by alveolar macrophages
Germinated spores expose Beta-glucan and are HIGH RISK! - neutrophils are then recruited to the site!
This happens if the patient is immunosuppressed and can’t stop the spores from germinating! They grow and shed and then beta glucan is exposed and then there is an inflammatory response
Relevance of innate immunity for fungal infections is that if there are Tx that can impair innate immunity, then there is an increased risk for fungal infections. Examples of things that do that?
Immunosuppression for organ transplants.
TNFalpha blockers for inflammatory disorders (Humera)
What are some growth forms of fungi that cannot be cleared by phagocytosis?
Capsules
Titan Cells
Spherules
Hyphae
You will have unique adaptive immunity responses depending on the composition of the fungus.
In general, what is activated? (what type of Th response)
What type of thing is formed during infection?
Th1 = protective
Th2 = less effective
Antibodies are used to opsonize and complement activate (used for serological diagnosis)
Granulomas are formed
- integrates both the innate and adaptive arms
- is an attempt to wall off fungi that are difficult to kill
Granuloma layers: foamy macrophages epitheliod macrophages lymphocytes fibroblasts
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Fungi are heterotrohphs like animals - plants are autotrophs.
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Diaper rash is another example of an opportunistic infection.
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hyphae, titan cells and spherules are too large for phagocytosis
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th2 dominates in systemic fungal infection but th1 is more important for histoplasmosis, etc. - Especially for inflammation and neutrophil recruitment.
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What do current fungal tx target?
PM (ergosterol)
Cell Wall
DNA/RNA synthesis
What do polyenes do?
Example?
Bind ergosterol and form a pore Amphotericin B (Notorious for side-effects - try to avoid using because it sometimes binds to cholesterol instead and works on our cells)
What do triazoles do?
Examples? (3)
What do they end in?
AZOLE. Block ergosterol synthesis Most widely used prescription antifungals! Exs: 1) fluconazole 2) Voriconazole? 3) Posaconazole?
What do allylamines do?
Ex?
Block ergosterol synthesis
Ex: Lamisil for athlete’s foot (both have L in the name)
What do echinocandins do?
What do they end in?
3 agents?
Block glucan synthase (cell wall) END IN FUNGIN. (CAM) 3 agents: Caspofungin Andulafungin Micafungin
Example of an anti fungal that is a pyrimidine analog?
Flucytosine
Problem with flucytosine? (pyrimidine analog)
Resistance! use in combination
It is a fluoridated cytosine
Vaccines for fungals lag behind those for bactera/fungi
Most treatments therefore involve immune reconstitution for immunosuppressed individuals!
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