Flashcards in Exam #1: Clinical Mycology Deck (39):
How many species of fungi infect humans?
150 of 200,000
How can fungi cause disease?
- Intoxication i.e. through the production of microtoxins
○ Ergot alkaloids (bread fungi w/ ingestion leads to hallucinations)
○ Alfatoxin (peanut butter fungi that is hepatotoxic)
○ Stachybotrys (black mold in homes that produces neurotoxin)
○ Recreational "shrooms"
- Allergens to mold spores
- Colonization & Disease i.e. when fungi colonize us causing disease
Describe the general characteristics of Fungi.
- Eukaryotic pathogen i.e. contains membrane bound organelles
- Very similar to human cells, making fungi challenging to treat (fewer targets for therapy) w/ two important differences:
○ Cell wall (that is also different from bacteria)
○ Membrane sterol composition (ergosterol vs. cholesterol)
Which fungi contains a capsule?
What are the functions of the fungal cell wall?
- Protection from osmotic shock
Describe the structure of the fungal cell membrane.
- Typical phospholipid bilayer
- Unique sterol composition that contains "ergosterol (instead of cholesterol)," which serves as the chemotherapeutic target of antifungal drugs
What are the two general categories of fungi?
- Molds (stuff growing on counter, refrigerator, strawberries)
Fungi that can grow as both yeast & molds--many pathogenic fungi are dimorphic
List the characteristics of yeast.
- Spherical or ellipsoid shape
- Reproduce by budding (buds are called "blastoconidia")
- Some form pseudohyphae
What is a pseudohyphae?
Pseudohyphae= when yeast buds never really separate; chains of buds that look like hyphae in mold
What is a germ tube?
Germ Tube= a characterstics pseudophphae that looks like a bud w/ long extension or spoon
- Canida albicans can form a "germ tube" in the presence of serum
What are the different structures that mold can form?
- Hyphae= individual strands of mold
- Mycelium= a mass of intertwined hyphae
○ Can be vegetative or aerial
- Septa= cross-walls that divide the hyphae into segments
How can mold reproduce?
- Sexually= spores
- Asexually= conidia
○ Micro= small
○ Macro= big
○ Chlamydo= spore formed in strand of hyphae
How are mold infections diagnosed?
Visually--there aren't many biochemical tests for mold (vs. bacteria)
What are the different types of fungal infections?
- Superficial mycoses= infection of the outermost layers of skin & hair
- Cutaneous mycoses= infection which extends deep into the epidermis as well as invasive hair & nail infections
○ Most common
- Subcutaneous mycoses= infections involving the dermis, subcutaneous tissues, muscle, & fascia
- Systemic mycoses= infections that originate in the lung but may spread to any organ in the body
- Opportunistic mycoses= infection associated with immunosuppressed individuals
What is the host response to fungal infection?
- Innate immune system= generally sufficient to prevent infection
○ Intact skin
○ Competition w/ normal bacterial flora
○ Epithelial turnover
○ Dissicated (dry) nature of stratum corneum
○ Mucous membranes have antimicrobial peptides & ciliated cells
- Neutrophils & macrophages are both capable of destroying or damaging fungal spores or hyphae
What is the role of the adaptive immune system to fungal infection?
- Cell-mediated (T-cell) is important (esp. INF-gamma production)
- Humoral (Antibody) plays a very small role
How do antifungal drugs differ from antibacterial drugs?
- Fewer antifungals available b/c of similarity to human cells
- Drugs are more toxic
What are some of the targets of antifungal drugs?
B-Glucan & Ergosterol (Cell wall & plasma membrane)
What is Squalene epoxidase?
Squalene epoxidase= enzyme involved in ergosterol synthesis
What class is amphotericin B?
- Polyene (binds to ergosterol & directly disrupts by causing a pore to form in the membrane-->osmotic disruption)
- Formerly the only polyene
What is the mechanism of echinocandins?
Cell wall synthesis inhibitors (B-glucan)
What is the limitation of the echinocandins?
Can only be used for fungi w/ a high concentration of B-glucan in cell wall
What is the problem with visual diagnosis of fungal infections in the lab?
Lots of mold in the environment can lead to contamination of the sample
How is the KOH prep used to identify fungi infection? What tissues is it good for?
- Skin, nail, hair...etc.
- KOH dissolves skin, hair...etc. cells at a greater rate than the fungal cells
○ Then add a dye to better visualize the actual fungi in the sample
Do fungi stain gram negative or gram positive?
What is the India ink stain used to identify? Why is this test important?
Cryptococcus neoformans, which is the cause of cryptococcal meningitis
What is the germ tube test used to identify?
In the lab, can you use the same agar to grow bacteria to grow fungi?
What are the two ways that fungal cells differ from human cells?
1) Presence of a rigid cell wall
2) Composition of the cell membrane (ergosterol)
How does the composition of the fungal cell wall differ from the bacterial cell wall?
Bacteria= peptidoglycan & teichoic acid
Fungus= mannan, glucan, chitin
What is the difference between septate & nonseptate?
Septate= segmented mold with septa
Nonseptate= nonsegmented mold without septa i.e. aseptate mold
What is the difference between conidia & spores?
Fungi reproduce both sexually & asexually.
- Conidia= reproductive units produced asexually
- Spores= reproductive units produced sexually
What is the mechanism of action of the azoles?
Inhibit ergosterol synthesis, which has a fungistatic effect
What is the mechanism of action of the nucleoside anagoles (5-flurocytosine)?
Inhibition of both RNA & DNA function & synthesis
What family of antifungals is activate against most medically important yeast, but NOT mold or dimorphic fungi?
Nuceloside analogs (5-flurocytosine)
What is the target of the Grisan family of antifungals? What type of infection would best be treated with a drug in the Grisan family?
- Inhibits microtubular function
- Best for superficial mycoses esp. scalp infection
What is the general mechanism of the Allylamines, Thiocarbamates, & Morpholines?
Inhibition of ergosterol synthesis