Micro 7 -- Clinical Mycology

What are the two primary methods that Fungi act as agents of disease? What is the broad method of action?

1. Mycotoxins (ex. ergot alkaloids = Salem witch trials, aflatoxin, recreational) 2. Allergens Method of action involves colonization

Under the right conditions, yeast can adopt two alternative structures, what are they?

1. Pseudohyphae = modified budding process, buds remain attached to original yeast and can for a chain 2. Germ tube = Pinocchio nose

Function of the fungal cell wall? How much of the cell mass is found within the cell wall?

1. Shape 2. rigidity 3. strength 4. protection from osmotic shocks 90% of cell mass is the cell wall

What are the two major structural classifications of fungi. What do they look like? Can some fungi grow as both?

1. Yeast (look like soccer/footballs 2. Molds (look fluffy or like ribbons) Yes, dimorphic fungi can grow as both/either

Compare how fungi can interact with humans, commensal, symbiotic and parasitic

1. commensal = no benefit or harm to humans 2. Symbiotic = mutually beneficial 3. Parasitic = disease

What are the most common targets of antifungals?

1. inhibit Cell wall 2. inhibit cell membrane 3. direct cell membrane damage

What factors determine the severity of disease caused by fungi?

1. size of inoculum 2. magnitude of tissue destruction 3. ability of fungi to multiply in tissue 4. immune status of host

Why are immunosuppressed patients, AIDS patients and people with T-Cell and neutrophil deficits more susceptible to fungal infections?

All these conditions compromise cell mediated immunity, the primary immune response to invading fungi

Compare the composition of bacterial cell wall to fungal cell wall

Bacterial cell wall = peptidoglycan Fungal cell wall = Chitin, Chitosan, cellulose, Glucan, Manna

What is the method of action of Amphotericin B (polyene)?

Binds to ergosterol in the fungal cell membrane Essentially binds to ergosterol and punches a hole in it, forming a pore that allows fluid to enter cell membrane and cause membrane to swell and pop

*Which particular fungi is the germ tube test specific for?

Candida albicans

Which plays a larger role in fungal immunity, antibodies or cell mediated immunity?

Cell mediated immunity

*Which particular fungi is the india ink stain test specific for? What does it detect?

Cryptococcus neoformans Detects the presence of a capsule (only fungi that has a capsule)

What is the primary diagnostic method of fungal infections?

Direct visualization of fungal elements

REVIEW: Which of the following drugs inhibits cell wall synthesis? Allylamines, Polyenes, Echinocandins, Azole derivatives, Morpholines

Echinocandins (the rest of the drugs all have to deal with the cell membrane)

Why are there fewer available antifungal drugs relative to antibacterials?

Fewer differences between fungi cells (eukaryotes) and human cells than between bacterial cells (prokaryotes) and human cells Not as many unique targets

What are the two primary differences between fungal cells and human cells?

Fungal cells have 1. Cell Wall 2. different cell membrane sterol composition (not cholesterol like humans)

Why are antifungal drugs more toxic to the host than antibacterial drugs?

Fungi have fewer unique characteristics than bacteria, so drugs that combat fungi are more likely to also have effects on host cells

Compare the growing speed and temp for fungus to bacteria

Fungus = grow slower, grow at lower temp (closer to room temp)

Compare the main sterol composition of human and fungi cell membrane

Human cell membrane = primarily cholesterol Fungi cell membrane = primarily ergosterol

Compare the difference in mold structure between hyphae, mycelium and septa

Hyphae is the general structure for molds, fluffy ribbon like. Mycelium is a large cluster of hyphae Septa are distinguishable segmentations of hyphae

What is the target of Echinocandins (caspofungin, andidula fungi)? Why are these drugs highly selective?

Inhibit B-glucan synthesis (a primary component of fungi cell walls) Highly selective because it doesnt affect human cells (no cell walls)

What form of host response is generally sufficient to prevent fungal infections? What must happen for fungi to gain access to, colonize and multiply in host tissues

Innate immunity (namely physical barriers to fungal infection) The host protective barriers must be breached for colonization to happen

What is the primary technique to visualize fungi of superficial infections, hair, nails, skin scrapings etc?

KOH Prep

**What type of antifungal is amphotericin B? What does it target?

Polyene Targets bind to ergosterol

*REVIEW: Which of the following antifungal drug does not target ergosterol biosynthesis? Allylamines, Polyenes, Thiocarbamates, Azole derivatives, Morpholines

Polyenes (Polyenes bind to ergosterol, they dont target ergosterol biosynthesis)

Differentiate between the following types of fungal infections: Superficial, cutaneous, subcutaneous, systemic, and opportunistic

Superficial = Infection of outer most layers of skin and hair Cutaneous = infection which extends into epidermis, as well as invasive hair and nails Subcutaneous = infection involving the dermis, muscle and fascia Systemic = infections that originate primarily in lung but may spread to any organ of the body Opportunistic = infections associated with immunosuppressed individuals

*What is the target of Allylamines, Thiocarbamates, and Morpholines?

Targets Ergosterol biosynthesis

*What is the target of Azole derivatives (ex. fluconazole, miconazole)

Targets Ergosterol biosynthesis

Compare the relative use of topical antifungals vs systemic antifungals

Topical antifungals are appropriate for superficial and most cutaneous infections Systemic antifungals are appropriate for subcutaneous and systemic infections

What is the difference between vegetative or aerial mycelium

Vegetative mycelium are colonies of yeast that grow into the substrate (ex. blue cheese) Aerial mycelium are colonies of yeast that grow above the substrate

Do fungi stain gram positive?

YES, cant differentiate between fungi and gram positive bacteria

Compare the method of reproduction between yeast and molds

Yeast = budding (asexual) Molds = conidia (asexual) and spores (sexual) (sexual vs asexual prob not important)

Compare the number of cells of yeast and molds

Yeast = spherical or ellipsoid (think soccerball/football) Molds = hyphae or septa

There are around 200,000 species of fungi, how many infect humans?

about 150