🍄 Fungal Biology
Core features
- Eukaryotes
- True nucleus
- 80S ribosomes
- Mitochondria
- Cell wall made of polysaccharides
- Chitin
- β-glucan
- Mannan
- Membrane sterol is ergosterol
- Azoles block its synthesis
- Polyenes bind it preferentially over cholesterol
Growth forms
- Hypha = filament; mycelium = mat of hyphae
- Yeast = single round to oval cell
- Pseudohypha = chain of elongated yeast with constrictions (Candida)
- Thermal dimorphism
- Mold at about 25 °C (environment)
- Yeast at 37 °C (tissue)
| Hyphae | Septa | Width | Branching | Example |
|---|---|---|---|---|
| Septate | Present | Even, tube-like | Acute (about 45°), dichotomous | Aspergillus |
| Nonseptate | Absent or rare | Broad, irregular, ribbon-like | Wide (about 90°) | Mucor, Rhizopus, Absidia |
Dimorphic pathogens
HistoplasmaBlastomycesCoccidioidesParacoccidioidesSporothrix
Spore types
| Spore | Origin | Context |
|---|---|---|
| Conidia | Asexual, borne on hyphae | Airborne, common |
| Blastoconidia | Buds on yeast | Yeast replication |
| Arthroconidia | Hypha fragments at joints | Dermatophytes, Coccidioides mold |
| Endospores in spherules | Inside a tissue sphere | Coccidioides tissue form |
Exam trap
- Pneumocystis is classified as a fungus despite lacking ergosterol-based drug responses.
🔍 Laboratory Diagnosis
Direct microscopy→Culture→Antigen / serology→Molecular probes
| Preparation | Appearance | Notes |
|---|---|---|
| KOH mount | Hyaline (colorless) or pigmented elements | Digests human cells, leaves fungi |
| PAS | Magenta-pink | General fungal stain |
| Silver stain | Gray to black | Pneumocystis cysts |
| Calcofluor white | Bright blue-white | Needs fluorescence microscope |
| India ink (CSF) | Clear halo around yeast on dark field | Cryptococcus; misses about half; positive rules in |
Culture
- Takes days to weeks
- Sabouraud agar with antibiotics
- Inhibitory mold agar
- Blood agar with antibiotics
- Colony and microscopic morphology identify the species
Other tools
- Antigen detection
- Cryptococcal capsular polysaccharide in CSF or serum
- Latex agglutination or counter-immunoelectrophoresis
- Serology
- Antibody screen
- Complement fixation
- Skin test
- Mainly epidemiologic; shows exposure only
- Anergy to a known infecting fungus = poor prognosis
- Blood culture useful for Histoplasma (lives in reticuloendothelial cells)
🧴 Superficial & Cutaneous Mycoses
Malassezia furfur Lipophilic yeast, skin commensal
- Pityriasis (tinea) versicolor
- Keratin-layer infection
- Favored by warm, humid climate
- Discolored patches on trunk and back
- KOH: round yeast clusters plus short curved hyphae
- Wood lamp: coppery-orange glow
- Treat: topical selenium sulfide or topical azole
- Fungemia in premature infants given IV lipid emulsions
Dermatophytes Trichophyton, Microsporum, Epidermophyton
- Filamentous, monomorphic
- Confined to skin, hair, nails
- Never disseminate
- Itching is the usual symptom
| Genus | Skin | Hair | Nails |
|---|---|---|---|
| Trichophyton | Yes | Yes | Yes |
| Microsporum | Yes | Yes | No |
| Epidermophyton | Yes | No | Yes |
| Tinea | Site |
|---|---|
| Capitis | Scalp; favus is severe, contagious, scarring alopecia |
| Barbae | Beard area |
| Corporis | Glabrous (hairless) skin |
| Cruris | Groin |
| Pedis | Feet |
| Unguium | Nails |
- Strongly inflamed lesion → usually animal source (zoophilic)
- Mildly inflamed lesion → usually human source
- Diagnosis
- KOH of scrapings shows hyphae and arthroconidia
- Microsporum glows yellow-green under Wood lamp
- Treatment
- Topical azole or tolnaftate
- Oral azole or griseofulvin for hair or extensive disease
- Keep skin dry
- Id reaction (dermatophytid) = allergic rash at a distant site from circulating antigen
Candida skin disease
- Cutaneous or mucocutaneous forms
- Can spread in compromised hosts
- Detailed in the opportunists card
🌹 Subcutaneous Mycosis
Sporothrix schenckii
- Dimorphic
- Mold form: hyphae with rosette-like conidia on plant matter
- Tissue form: cigar-shaped yeast
- Entry: skin puncture from thorns, splinters, sphagnum moss
- Lymphocutaneous (rose gardener) sporotrichosis
- Nodules track up the lymphatics
- Treat: itraconazole; potassium iodide is an older option
- Pulmonary form
- Seen with alcohol use disorder and homelessness
- Bone or joint disease: itraconazole
- Severe or systemic disease: amphotericin B
🫁 Endemic Systemic Mycoses
- Four dimorphic pathogens
- Histoplasma, Coccidioides, Blastomyces, Paracoccidioides
- Inhaled spores start lung infection
- Spectrum
- Acute pulmonary (most are silent or self-limited)
- Chronic pulmonary
- Disseminated
- Work-up
- Sputum cytology (calcofluor helps)
- Culture on special media
| Feature | Histoplasma capsulatum | Coccidioides immitis | Blastomyces dermatitidis | Paracoccidioides brasiliensis |
|---|---|---|---|---|
| Geography | Ohio and Mississippi river valleys | Southwestern US, San Joaquin Valley | Great Lakes, Ohio–Mississippi, Southeast, Canada | Central and South America, Brazil highest |
| Source | Soil with bird or bat droppings | Desert soil | Moist soil, rotting wood (uncertain) | Humid, acidic, vegetated soil |
| Mold form | Microconidia and tuberculate macroconidia | Hyphae breaking into arthroconidia | Hyphae with plain conidia | Septate hyphae, chlamydoconidia |
| Tissue form | Tiny yeast inside macrophages, narrow-necked buds, no capsule | Spherule filled with endospores | Large yeast, broad-based bud, thick double wall | Round yeast with many peripheral buds |
| Typical risk | Caves, chicken coops, starling roosts | Dust exposure, late pregnancy, AIDS | Outdoor soil exposure | Rural agricultural work |
| Treatment | Itraconazole mild; amphotericin B severe | Itraconazole or fluconazole mild-moderate; amphotericin B severe | Itraconazole mild-moderate; amphotericin B severe | Itraconazole; amphotericin B if refractory |
Histoplasmosis
- Facultative intracellular in reticuloendothelial cells
- Flu-like pneumonia
- Hepatosplenomegaly even in acute disease
- Healed lesions calcify
- Relapse with T-cell suppression
- Disseminated: mucocutaneous lesions, common in AIDS
Coccidioidomycosis
- Arthroconidia inhaled → round up → spherules → endospores
- Self-limited pneumonia
- Erythema nodosum and arthritis suggest good outcome
- Lung lesions calcify
- Dissemination: meningitis, skin, bone
- Immunocompromised and third-trimester pregnancy
Blastomycosis
- Acute and chronic pneumonia
- Less likely to resolve unaided
- Even acute disease is often treated
- Can disseminate (skin, bone)
Paracoccidioidomycosis
- Mostly subclinical
- Acute (juvenile): fever, nodes, hepatosplenomegaly, skin lesions
- Chronic (adult): lung fibrosis, bullae, emphysema (about 35%)
- Oral and cutaneous ulcers
High-yield
- Intracellular tiny yeasts in macrophages = Histoplasma.
- Broad-based budding yeast = Blastomyces.
- Spherule with endospores = Coccidioides.
- Multiple budding "mariner's wheel" yeast = Paracoccidioides.
⚠️ Opportunistic Fungi
Aspergillus fumigatus
- Monomorphic mold; soil, compost, decaying matter
- Septate hyphae, acute-angle dichotomous branching
| Syndrome | Setting | Features | Treatment |
|---|---|---|---|
| Allergic bronchopulmonary (ABPA) | Asthma, cystic fibrosis | Grows in mucus plugs; no tissue invasion | Glucocorticoids plus itraconazole |
| Aspergilloma (fungus ball) | Old lung cavities | Cough, hemoptysis | Surgical removal if bleeding; azole |
| Invasive | Neutropenia, CGD, burns | Vessel invasion → infarcts, hemorrhage; sinus to brain; burn cellulitis | Voriconazole |
Candida albicans
- Yeast of normal mucosal flora
- Germ tubes at 37 °C in serum
- Invasive disease shows pseudohyphae and true hyphae
- KOH shows budding yeast, pseudohyphae, hyphae
| Disease | Predisposition |
|---|---|
| Perlèche (angular cheilitis) | Mouth-corner creases, malnutrition |
| Oral thrush | Infancy, antibiotics, steroids, AIDS |
| Esophagitis, gastritis | Antibiotics, immunosuppression, AIDS |
| Candidemia | Cancer, IV catheters; endophthalmitis, nodular skin lesions |
| Endocarditis | Injection drug use |
| Intertrigo / diaper rash | Obesity, infants, occlusion |
| Vulvovaginitis | Diabetes, antibiotics |
| Chronic mucocutaneous | T-cell defects, endocrinopathy; anergy to Candida |
- Treatment
- Topical azole or nystatin for mucosal disease
- Fluconazole or amphotericin B for disseminated disease
- Echinocandins are first-line for many invasive infections
Cryptococcus neoformans
- Encapsulated, monomorphic yeast
- Source: soil with pigeon droppings
- Lung entry, often silent
- Leading fungal meningitis in AIDS; also lymphoma
- CSF diagnosis
- Capsular antigen test (most sensitive)
- India ink halos
- Culture: urease-positive yeast
- Treatment: amphotericin B plus flucytosine induction, then fluconazole
Mucorales Mucor, Rhizopus, Absidia
- Nonseptate, broad ribbon hyphae, right-angle branching
- Spores inhaled from soil
- Rhinocerebral disease
- Facial swelling, black necrotic tissue, bloody discharge, altered mentation
- Ketoacidotic diabetes, leukemia
- Spreads rapidly through tissue planes and vessels
- Treatment: urgent surgical debridement plus amphotericin B
Pneumocystis jirovecii
- Fungus by ribosomal RNA sequencing
- Extracellular organism, no routine culture
- Interstitial pneumonia
- Advanced HIV (low CD4)
- Malnourished or premature infants
- Other immunocompromised hosts
- Fever, dry cough, dyspnea
- Foamy alveolar exudate on H&E
- Silver stain highlights cysts in the exudate
- Imaging: bilateral ground-glass, diffuse infiltrates
- Diagnosis: silver stain of lavage fluid or biopsy
- Treatment: trimethoprim-sulfamethoxazole; dapsone is an alternative
Clinical warning
- Azole resistance is rising in Aspergillus, Candida and Cryptococcus.
💊 Antifungal Drug Map
| Drug class | Mechanism | Main uses | Key toxicity |
|---|---|---|---|
| Amphotericin B (polyene) | Binds ergosterol, forms membrane pores | Severe endemic mycoses, Mucorales, cryptococcal meningitis | Nephrotoxicity, infusion reactions, hypokalemia |
| Nystatin (polyene) | Same as above | Topical thrush | Minimal (not absorbed) |
| Azoles | Inhibit ergosterol synthesis (14α-demethylase) | Candida, dimorphic fungi, Aspergillus (voriconazole) | Hepatotoxicity, CYP450 interactions |
| Echinocandins | Block β-glucan synthesis | Invasive Candida, Aspergillus salvage | Infusion reaction, liver enzyme rise |
| Flucytosine | Converted to 5-FU, blocks DNA/RNA synthesis | Cryptococcus (with amphotericin B) | Bone marrow suppression |
| Terbinafine | Inhibits squalene epoxidase | Dermatophyte nail infection | Hepatotoxicity |
| Griseofulvin | Disrupts microtubules, deposits in keratin | Tinea capitis | Hepatotoxicity, CYP induction |
Clinical pearl
- Mild endemic mycosis gets an azole; severe disease starts with amphotericin B.