Medical mycology

Fungal structure: 

Spore sexual: asco, basidio, zygo 

Spore asexual: conidia, sporangiospores 

Hypha

Pseudohyphae 

Coneocyte 

Septa 

Mycelium 

Cell wall: chitin, beta glucans, mannans, glycoprotein 

Cell membrane: ergosterol 

Acquisition → adhesion/colonization → invasion → immune evasion/proliferation → damage 

Routes of infection: ✓

Inhale 

Trauma/inoculation 

Colonization overgrowth 

Ingestion 

Thermotolerance = able to grow at 37°C 

Virulence factors 

1. Structural factors 

Capsule: galactoxylomannan induces T cell apoptosis, glucoxylomannan inhibit phagocytosis 

Melanin - uv, free radicals 

2. Enzymatic factors 

Protease degrade collagen, elastin, IgA by candida 

Phospholipase disrupt membrane by candida, cryptococcus 

Urease alkalinize environment by cryptococcus 

3. Morphological factors  ✓

Dimorphism 

Biofilms 

Phenotypic switching = white-opaque changing 

- drug susceptibility: opaque cells more susceptible to some antifungals 

4. Adhesins 

Colonization 

Invasion 

Biofilm foundation 

Endothelial adherence trigger 

Agglutinin like sequence, hyphal wall protein 1 by candida albicans target epithelium 

5. Immune evasion PINA IC

Pre phagocytic evasion - inhibit phagocytosis 

IC survival - in phagosome 

Non lytic exocytosis - vomocytosis 

Antigen variation - white-opaque 

Immune masking - candida hides beta glucans under mannoprotein 

Cytokine modulation - induce Th2/Treg response 

Fungal disease spectrum: 

1. Dermatomycoses 

Pityriasis versicolor 

Malassezia furfur 

Scaly, macular lesions 

Upper torso, arms, legs, abdomen 

Hyphae & yeast = spaghetti & meatballs 

Black piedra 

Piedraia hortae (ascomycete)

SDA dark colonies 

White piedra 

Trichosporon beigelii

Hair with white soft nodules 

Axilla or scalp 

Hyphae, arthroconidia, blastoconidia after KOH treatment 

Tinea nigra 

Exophiala wernickii (dimorphic)

Brown to black macular lesions on palms and soles 

Darkly pigmented yeast like cells, hyphae 

Onchomycosis 

Tinea unguium 

Discoloration, thickening, separation from nail bed 

Dermatophytosis/ringworm 

Tinea capitis, cruris, pedis 

Direct contact with skin scales 

KOH treatment - hyphae, arthroconidia 

2. Subct mycoses 

Sporotrichosis ✓

Sporothrix schenckii - rose thorns, hay

Conidia enter trauma ✓→ granulomatous nodules → necrosis/ulcer → lymphatic drainage pattern 

Cigar shaped budding yeast

Chromoblastomycosis 

Fonsecaea, Cladophialophora 

Sclerotic bodies resist phagocytosis 

Mycetoma 

Madurella 

Hyphae aggregate in tissue 

3. Systemic/endemic mycoses inhale conidia ✓

Histoplasmosis 

Histoplasma capsulatum 

Inhale conidia → yeast in lungs → ingest by alveolar macrophage → calcified granulomas → suppress cell-mediated immunity → disseminate to liver spleen BM 

Thermally dimorphic 

Sputum/tissue 

Tuberculate chlamydospores in culture 25°C 

Histoplasma Ag in urine 

Coccidioidomycosis 

Coccidioides immitis 

Inhale arthroconidia → spherules in lungs → rupture, release endospores → disseminate 

Sputum/tissue 

↑ IgM (recent), IgG (disseminate) - serology 

H&E

Cannot culture as hazardous 

Blastomycosis 

Blastomyces dermatitidis 

Mass-like lung opacities like cancer 

Thermally dimorphic 

Inhale conidia → yeast in lungs → abscess → granulomas → rarely disseminate to skin, bone 

Sputum/skin lesions 

Broad base bud yeast 

No serology 

Para coccidioidomycosis 

Para coccidioides brasiliensis 

Thermally dimorphic 

Inhale conidia → yeast in lungs → disseminate 

Yeast with multiple buds

Double agar gel immunodiffusion 

4. Opportunistic mycoses 

Candidiasis ✓

Candida albicans - catheter related 

Germ tubes in serum 37°C + thick wall vesicles 

Not dimorphic 

Direct contact 

Local invasion 

Thrush, skin lesions 

Disseminated candidiasis 

Chronic mucocutaneous candidiasis 

Yeast, pseudohyphae 

Yeast only = colonization = gram positive 

Blood culture bottles 

Cryptoccocosis ✓

Cryptococcus neoformans in bird dropping 

Meningitis 

Not dimorphic 

Heavily encapsulated yeast 

Inhale yeast → ↓ cell mediated immunity → disseminate to CNS 

India ink of CSF 

Single encapsulated yeast cell budding with clear halo 

Blood culture bottles 

Mucicarmine histopathology - red capsule 

Aspergillosis ✓

Aspergillus fumigatus - dust construction/hospital 

Allergic bronchopulmonary aspergillosis (IgE antibodies 

Aspergilloma (fungus ball in lung cavity - IgG precipitin/immunodiffusion test 

Mold with septate hyphae V angle 

Not dimorphic 

Inhale conidia → swell in alveoli → germinate → hyphae spread through pung parenchyma & blood vessel → necrosis & hemorrhage → disseminate 

Septate hyphae 

Mycelium on Sabourand dextrose agar 

Small, fluffy white/green colonies, sporulation within 2 days 

Galactomannan positive (use serum

PCR 

Mucormycosis 

Mucorales: Mucor, Rhizopus 

Molds with non septate hyphae 90°C 

Not dimorphic 

Inhale spores →germinate in sinus & lungs → hyphae invade tissue → angioinvasion → necrosis + infarction 

DKA, leukemia 

Isolation through culture 

Biopsy + histopathology 

No Ag test

Talaromycosis = TB, leishmaniasis, cryptoccocosis 

Talaromyces marneffei

Papular skin lesions 

Dimorphic 

Diffusible red pigment in culture 

Hyalohyphomycosis 

Hyaline molds: Fusarium, Scedosporium, Acremonium, Paecilomyces 

Inhale spores/localized ct lesions 

No pigmented, septate, branching, filamentous 

Neutropenic patients 

Culture 

Voriconazole treatment 

Pneumocystis jirovecii ✓

PCR 

GMS 

No culture 

Diagnosis for pan fungal: microscopy, culture,PCR, antigen, histopatho ✓

calcofluor white microscopy = fluorescent under UV 

Beta-D-glucan Ag except crypt and mucorales ✓ 

Pan fungal PCR ✓

GMS silver histo: black fungi against green background 

H&E