Fungi Flashcards
Morphologic characteristics of Aspergillus
Dichotomous (Y-shaped) branching and septated
Morphologic characteristics of Zygomycetes
Right angled (T-shaped) branching and non-septated
Morphologic characeristics of candida albicans
Hyphae, pseudohyphae, budding yeast (this triad is diagnostic of candida!)
If also germ tube positive = candida albicans
Morphologic characteristics of Malassezia
Clusters of yeast and strands of hyphae (spaghetti and meatballs)
Definition of dimorphism
Fungus exists in nature and room temp as a filamentous fungus (mold) and converts to yeast in tissue (NOTE that candida is the reverse)
Components of fungal cell wall
1-3 beta glucans, 1-6 beta glucans, mannans, chitin
Primary treatment for Zygomycetes
Amphotericin B
Primary treatment for Aspergillus
Voriconazole
Best stains for detecting fungi
Periodic acid-Schiff (PAS) and Gomorri’s Methenamine silver (GMS)
And always H&E
Presentation of Sporotrichosis
Subcutaneous, lymphocutaneous distribution, dimorphic pathogen, common in Maryland area when in contact with plants.
But other things present similarly so make sure to ask where person has been!
Superficial infections
Tinea versicolor
Mucocutaneous infections
Dermatophytosis, mucocutaneous candidiasis
Subcutaenous infections
Chromoblastomycosis, mycetoma, sporotrichosis
Deep mycosis
Opportunistic (candidiasis, aspergillosis, zygomycosis) and pathogenic (histoplasmosis)
What is the difference between conidia and sporangiospores?
Both are asexually produced propagation structures of fungi (what we actually inhale), but sporangiospores are from zygomyces and conidia are from aspergillus and all other fungi
Possible virulence factors of fungi
Cell surface receptors Hydrolytic enzymes Host mimicry Polysaccharide capsule Melanin production (inhibits oxidative killing mechanisms)
What fungus has budding yeast and is encapsulated?
Cryptoccocosis
What molecule makes up the lipid portion of fungal cell membrane?
Ergosterol
What components of fungal cell wall can be detected in culture and used to diagnose fungal infections?
1-3 B glucan, mannas, galactomannan
What is the fundamental way in which many antifungal agents work?
Interrupting erogsterol biosynthesis
What are the main targets of antifungal agents in the pathway of ergosterol biosynthesis, and which antifungal agent affects each target
Squalene epoxidase - allylamines
Lanosterol 1,4 a-demethylase - azoles
Ergosterol itself - Ampho B
Mechanism of action of Ampho B
Binds directly to ergosterol in cell membrane to form ionic pores
Toxicity of ampho B
Kidney
Spectrum of Ampho B
Yeasts and moulds (filamentous fungi)
Mechanism of action of Azoles
Inhibit cytochrome P-450 dependent enzymes (lanosterol C14-demethylase) required to synthesize ergosterol
Toxicity of Azoles
Hepatic
Spectrum of Azoles
Yeasts and moulds (filamentous fungi)
What is the major azole used to treat aspergillus?
Voriconazole
What is the major azole used to treat candida and cryptococcus?
Fluconazole
Mechanism of action of echinocandins
Target fungal cell wall biosynthesis of 1-3 beta-glucans
Toxicity of echinocandins
Hepatic
Spectrum of echinocandins
Only Candida and Aspergillus (primary agents against Candida!)
Mechanism of action of 5-fluorocytosine (5-FC)
Inhibit synthesis of DNA and RNA (similar to the 5-FU used in cancer therapy)
Toxicity of 5-FC
Hepatic
Spectrum of 5-FC
Cryptococcus (primarily causes meningitis so this is primary agents against it)
Mechanism of action of Allylamines (Terbinafine)
Inhibits squalene epoxidase and ergosterol synthesis
Toxicity of Terbinafine
Hepatic
Spectrum of Terbinafine
Dermatophytes
What is the primary treatment for cryptococcal meningitis?
Ampho B + 5-FC
What is the most superficial mycoses?
Tinea versicolor
What are the cutaneous mycoses?
Dermatophytoses and onchomycosis
What are the most common dermatophyte organisms?
Epidermophyton floccosum, Microsporum, Trichophyton
Dermatophyte infection of the foot?
Tinea pedis
Dermatophyte infection of the capitis?
Tinea capitis
Dermatophyte infection of the body?
Tinea corporis
Dermatophyte infection of the groin?
Tinea cruris
Dermatophyte infection of the nail?
Tinea unguium
Dermatophyte infection of the hand?
Tinea manuum
Which dermatophyte causes tinea pedis?
Trichophyton rubrum
Which dermatophyte causes tinea capitis?
Trichophyton tonsurans
Which dermatophyte predominates in US?
Trichophyton
Which dermatophyte predominates in the rest of the world?
Microsporum
Which tinea does Microsporum not cause?
Tinea ungugium (nails)
Which dermatophyte causes tinea cruris?
Epidermophyton floccosum
What is “black dot” alopecia?
Kerion forms where hair broke, get increased cell-mediated immune response
What are the different mechanisms of hair invasion?
Ectothrix invasion - outside hair shaft, cuticle destroyed. Endothrix invasion - within hair shaft, cuticle intact.
What is the primary method of diagnosis?
KOH or calcofluor preparation of scrape from leading edge of lesion
What is the treatment for tinea capitis?
Oral antifungals (terbinafine, intraconazole); ketoconazole shampoo; selenium sulfide lotion for family members
What is the treatment for tinea pedis, tinea corporis, tinea cruris, tinea manuum?
Topical antifungals (miconazole, clotrimazole, etc.); oral antifungals given if infection is extensive/severe
What is onychomycosis?
Infection of nail plate/nail bed
What causes onychomycosis?
Dermatophytes, usually Trichophyton rubrum. Increased risk in diabetics, HIV/AIDS, other compromised hosts
Why is good foot care essential for diabetics?
If onychomycosis develops on toenail and penetrates into skin, can cause staph infection. Staph infection -> osteomyelitis -> amputation
Three clinical types of onychomycosis
Proximal subungual (PSO), distal subungual (DSO), white superficial (WSO)
Which is the most common type of onychomycosis?
DSO
Mechanism of invasion of DSO
Hyphae enter distally under nail plate and spread proximally, digesting stratum corneum of nail bed and nail plate
Mechanism of invasion of PSO
Infection enters at cuticle and involves proximal nail bed, can spread distally
Mechanism of invasion of WSO
Dorsal surface of nail plate is attacked, minimal inflammation as viable tissue not involved
Treatment for onychomycosis
Oral therapy (terbinafine, intraconzole)
What causes tinea versicolor?
Malassezia furfur
Treatment for tinea versicolor
Topical: econazole, ketoconazole, or selenium sulfide shampoo; Short course oral: itraconazole, fluconazole
Dermatophytes from what source will cause muted inflammatory response?
Anthropophilic species (like T. tonsurans) because the immune system recognizes these as self
Which dermatophyte causes tinea cruris?
Epidermophyton floccosum
What is an early indicator of HIV infection?
Proximal subungual onchomycosis (PSO)
What is the difference between opportunistic and pathogenic mycoses?
Opportunistic - only occur in compromised hosts; pathogenic - occur in host no matter the state of the immune system
What are the morphological characteristics of candida?
Hyphae, pseudophyphae, budding yeast
Treatment for mucocutaneous candidiasis
Topical azoles, or oral fluconazole
What predisposes an individual to mucocutaneous candidiasis?
Immunosuppression by underlying diseases (HIV, diabetes), steroids, pregnancy, age, and receiving antibiotics
What predisposes an individual to invasive candidiasis?
Usually seen in hospitalized patients (altered barriers like catheters, trauma, etc.); unresponsive to antibacterial antibiotic
Pathogenesis of invasive candidiasis
Adherence and colonization
Penetration through barrier and angioinvasion
Hematogenous dissemination
Organ seeding
Replication in tissue yield necrosis +/- abscess formation with budding yeast and hyphae present
Treatment of invasive candidiasis
First line - echinocandins, then fluconazole
What clinical diseases are associated with Aspergillus?
Toxins, allergic syndromes, colonization (old TB cavity), infections (keratitis, invasive disease)
Pathogenesis of invasive aspergillosis
Inhalation of conidia
Compromised host cannot phagocytose with macrophages
Germination of conidia with hyphal invasion of lung parenchyma
Angioinvasion with thrombus formation and tissue necrosis
Hematogenous dissemination from lung to elsewhere
Morphological characteristics of Candida albicans?
Hyphae, pseudohyphae, and GERM TUBE
Morphological characteristics of Aspergillus?
Septated, branching hyphae
Treatment for Aspergillus?
Voriconazole, or liposomal AmphoB
Pathogenesis of Zygomycosis
Inhalation/contact with sporangiospores (asexual spores)
Infection in paranasal sinuses
Tissue invasion of nerves and blood vessels may eventually invade orbit and eye
Direct extension of invasion to brain
Morphological characteristics of Zygomycosis
Wide, nonseptated hyphae that branch at right angles (T shape)
What clinical disease is frequently caused by Cryptococcus neoformans?
Meningioencephalitis
What patients are at risk for Cryptococcus neoformans infection?
T cell compromised patients (on high dose steroids, on immunosuppressive agents, HIV+ patients with low CD4 count)
Pathogenesis of Crytococcosis
Inhale yeast
Replicate in lung and recruit CD4, CD8 cells
Can clear pulmonary infection, but can also results in hematogenous dissemination across BBB
Replicate yeast and form gelatinous lesion
Breakdown meninges
Morphological characteristics of Cryptococcus neoformans
Spherical yeast cells, pinched attachment between mother and daughter cells
Capsulated
What is the capsule of Cryptococcus composed of?
Glucuronoxylomannan (used as antigen for rapid diagnosis)- Inhibits intracellular phagocytosis
What is phenoloxidase
Enzyme in production of melanin, specific for C. neoformans
Treatment for Cryptococcus
Ampho B plus 5-FCCan use fluconazole for maintenance
Treatment for Pneumocystis carinii
Trimethoprim-sulfamethoxazole
What are the fungi that cause deep mycoses?
Histoplasma capsulatum
Coccidiodes immitus
Blastomyces dermatitidis
Paracoccidiodes brasilensis
Where is Histoplasma capsulatum found?
Soil and caves with bird or bat fecal material
Ohio-Mississippi river valley regions
Where is Coccidiodes immitis found?
Desert soil in SW USA
Sonoran valley climates in Latin America
Where is Blastomyces dermatitidis found?
Water in North Central and SE USA
How do deep mycoses enter host?
Inhalation of asexual spores
Not transmitted person to person
How does Histoplasmosis present?
- 90-95% have asymptomatic or mild respiratory symptomology
- Disease of reticuloendothelial system - liver, spleen, lymp nodes, bone marrow, adrenals
Pathogenesis of Histoplasmosis?
Inhalation of asexual spores (microconidia)
Conversion to yeast phase
Phagocytosed, but not killed, by alveolar macrophages
Replicate in macropage
Go to visceral organs and spread, especially if immunocompromised and can’t form granuloma
Normal v. immunocompromised host presentation of Histoplasmosis (compare them)
Normal host - granulomas produced
- Can have necrosis (caseous necrosis) so almost indistinguisable from TB
Immunosuppressed host - no well formed granulomas, many intracellular yeasts in each macrophage
Morphological characteristics of Histoplasma
3 um budding INTRACELLULAR yeast - in cytoplasm of macrophages, histiocytes, and lymphocytes
Morphological characteristics of Blastomyces dermatidis
Large yeast with thick double refractal wall (no capsule), broad base budding
Morphological characteristics of Coccidiodes immitis
Spherules
What is the treatment for the deep mycoses?
Intraconazole (and can use fluconazole for Coccidiodes)
