Fungi

🟢 Lite — Quick Review (1h–1d)

Rapid summary for last-minute revision before your exam.

Fungi — Key Facts for NEET PG

• Fungal Cell Wall: Ergosterol (target of antifungal azoles and polyenes); NOT cholesterol (humans use cholesterol, so selective toxicity possible)
• Dimorphic Fungi: Exist as yeast (37°C) or mold (25°C) — e.g., Histoplasma capsulatum, Blastomyces, Paracoccidioides, Candida albicans
• Mycoses Classification: Superficial (tinea/dermatophytes), Subcutaneous, Systemic (opportunistic)
• Cryptococcus neoformans: Encapsulated yeast; India ink negative stain shows capsule; Found in pigeon droppings
• ⚡ Exam tip: Systemic antifungals: Amphotericin B (binds ergosterol, creates pores), Azoles (inhibit lanosterol 14-α-demethylase), Echinocandins (inhibit β-glucan synthase)

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🟡 Standard — Regular Study (2d–2mo)

Standard content for students with a few days to months.

Fungi — NEET PG Study Guide

Fungal Structure

Yeast: Single-celled, reproduce by budding (e.g., Candida, Cryptococcus)

Mold: Multicellular, thread-like filaments

Dimorphic fungi: Exist as either yeast or mold depending on conditions

Hyphae: Thread-like filaments forming mycelium

Septate hyphae: Cross-walls with pores (most fungi)

Aseptate (coenocytic) hyphae: No cross-walls (e.g., Mucor, Rhizopus)

Classification of Mycoses

Superficial: Ringworm (tinea), Pityriasis versicolor, Black piedra

Subcutaneous: Sporotrichosis, Chromoblastomycosis, Mycetoma

Systemic (Deep):

• Endemic: Histoplasmosis, Blastomycosis, Coccidioidomycosis, Paracoccidioidomycosis
• Opportunistic: Candidiasis, Aspergillosis, Cryptococcosis, Zygomycosis, Pneumocystis (now P. jirovecii)

NCE Exam Pattern

Common question types:

1. Fungal morphology and classification
2. Superficial vs subcutaneous vs systemic mycoses
3. Dimorphic fungi characteristics
4. Antifungal mechanisms
5. Opportunistic fungal infections in immunocompromised

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🔴 Extended — Deep Study (3mo+)

Comprehensive coverage for students on a longer study timeline.

Fungi — Comprehensive NEET PG Notes

Detailed Theory

1. Fungal Cell Structure

Cell Wall:

• Primarily chitin (N-acetylglucosamine polymers)
• β-glucans (1,3 and 1,6)
• Mannoproteins (surface glycoproteins)

Cell Membrane:

• Ergosterol (target of many antifungals)
• Unlike human cholesterol

Cytoplasm:

• Nucleus with nuclear pores
• Mitochondria
• Ribosomes (80S)
• Endoplasmic reticulum
• Golgi apparatus

2. Fungal Reproduction

Asexual Reproduction:

• Budding: Yeasts (e.g., Candida)
• Conidiation: Mold spores (conidia) from conidiophores
• Sporangiospores: Within sporangia (e.g., Mucor)

Sexual Reproduction:

• Produces sexual spores (ascospores, basidiospores, zygospores)
• Important for classification

Fungal Identification:

• Colony morphology (color, texture)
• Microscopic morphology (hyphae, spores)
• Biochemical tests (urease, carbohydrate assimilation)

3. Superficial Mycoses

Dermatophytes (Tinea/ringworm):

• Trichophyton: Hair, skin, nails
• Microsporum: Hair, skin
• Epidermophyton: Skin, nails
• Clinical: Tinea capitis, corporis, cruris, pedis, unguium
• Diagnosis: KOH preparation, Wood’s lamp (some Microsporum)

Pityriasis (Tinea) Versicolor:

• Malassezia furfur (lipophilic yeast)
• Hypo/hyperpigmented macules on trunk
• “Spaghetti and meatballs” on KOH

Tinea Nigra:

• Exophiala werneckii
• Brown-black macules on palms

Black Piedra:

• Piedraia hortae
• Dark nodules on hair shaft

White Piedra:

• Trichosporon asahii
• White nodules on hair shaft

4. Subcutaneous Mycoses

Sporotrichosis:

• Sporothrix schenckii
• Dimorphic, “cigar-shaped” yeast in tissue
• Lymphocutaneous spread (rose gardener’s disease)
• Treatment: Itraconazole, potassium iodide (saturated solution)

Chromoblastomycosis:

• Fonsecaea, Cladophialophora, Phialophora
• Dark brown “sclerotic cells” in tissue
• Verrucous lesions
• Treatment: Itraconazole, flucytosine

Mycetoma (Maduromycosis):

• Actinomadura, Nocardia (bacterial), Fusarium, Madurella
• Swelling, sinus tracts, granules
• “Grain” color distinguishes causative agent
• Treatment: Prolonged azole therapy

5. Endemic (Geographic) Mycoses

Histoplasmosis (Mississippi/Ohio River valleys):

• Histoplasma capsulatum (dimorphic)
• Yeast form: Small (2-4 μm), intracellular in macrophages
• Bird/bat droppings (spelunker’s disease)
• Pulmonary → disseminated (AIDS)
• Diagnosis: Urine/serum antigen, Wright stain of biopsy

Blastomycosis (Ohio/Mississippi River valleys):

• Blastomyces dermatitidis (dimorphic)
• Broad-based budding yeast (8-15 μm)
• Pulmonary → cutaneous
• Verrucous skin lesions

Coccidioidomycosis (Southwestern US, Central/South America):

• Coccidioides immitis, C. posadasii
• Endemic to San Joaquin Valley (Valley fever)
• Spherules with endospores (tissue form)
• Primary pulmonary → disseminated (meningitis common)
• Diagnosis: Serology (IgM/IgG), spherules in tissue

Paracoccidioidomycosis (South America):

• Paracoccidioides brasiliensis (dimorphic)
• “Pilot wheel” or “Mickey Mouse” budding yeast (large)
• Mucocutaneous lesions
• Treatment: Itraconazole, sulfamethoxazole-trimethoprim

6. Opportunistic Mycoses

Candidiasis:

• Candida albicans (most common), C. glabrata, C. tropicalis, C. krusei
• Normal flora → opportunistic
• Mucocutaneous: Oral thrush, esophagitis, vulvovaginitis, Balanitis
• Systemic: Candidemia, hepatosplenic, endophthalmitis
• Risk factors: Immunosuppression, antibiotics, diabetes, catheters
• Diagnosis: Gram stain, KOH, culture on Sabouraud’s agar
• Germ tube test: C. albicans forms germ tube in 2-3 hours
• Treatment: Azoles (fluconazole), echinocandins (systemic)

Aspergillosis:

• Aspergillus fumigatus (most common), A. flavus, A. niger
• Mold with septate hyphae, 45° angle branching
• Allergic bronchopulmonary aspergillosis (ABPA): Type I and III hypersensitivity
• Aspergilloma: Fungus ball in pre-existing cavity
• Invasive aspergillosis: Angioinvasion, hemorrhagic infarcts (immunocompromised)
• Diagnosis: Galactomannan test, β-D-glucan, CT findings
• Treatment: Voriconazole (drug of choice), amphotericin B

Cryptococcosis:

• Cryptococcus neoformans (most common), C. gattii
• Encapsulated yeast (India ink shows capsule)
• Found in pigeon droppings, soil
• Pulmonary: Often asymptomatic
• CNS: Meningoencephalitis (AIDS-defining)
• Diagnosis: India ink (CSF), cryptococcal antigen (latex agglutination)
• Treatment: Amphotericin B + flucytosine (induction), fluconazole (maintenance)

Zygomycosis (Mucormycosis):

• Mucor, Rhizopus, Absidia (entomophthorales)
• Aseptate (or sparsely septate) hyphae, right-angle branching
• Rhinocerebral mucormycosis (diabetics, ketoacidosis)
• Pulmonary, GI, cutaneous forms
• Treatment: Amphotericin B, surgical debridement

Pneumocystis pneumonia (PCP):

• Pneumocystis jirovecii (formerly P. carinii)
• Despite name change, still fungal
• AIDS-defining illness
• Diffuse bilateral ground-glass infiltrates
• Diagnosis: Induced sputum, BAL (cysts on methenamine silver stain)
• Treatment: Trimethoprim-sulfamethoxazole (TMP-SMX)

7. Antifungal Agents

Polyenes:

• Amphotericin B: Binds ergosterol, creates membrane pores
  • “Gold standard” for serious systemic mycoses
  • Severe side effects: Nephrotoxicity, infusion reactions
  • Liposomal formulations (less toxic)
• Nystatin: Topical only (too toxic for systemic)

Azoles:

• Inhibit lanosterol 14-α-demethylase (ergosterol synthesis)
• Fluconazole: Candida (not C. krusei, some C. glabrata), Cryptococcal meningitis prophylaxis
• Itraconazole: Histoplasmosis, Blastomycosis, Sporotrichosis, Onychomycosis
• Voriconazole: Aspergillosis (drug of choice)
• Posaconazole: Mucormycosis, prophylaxis
• Ketoconazole: Androgen synthesis inhibition (gynecomastia)

Echinocandins:

• Inhibit β-(1,3)-D-glucan synthase (cell wall)
• Caspofungin, Micafungin, Anidulafungin
• Candida (including resistant strains), Aspergillus
• Fungicidal

Flucytosine (5-FC):

• Converted to 5-FU, inhibits DNA/RNA synthesis
• Used with amphotericin B for cryptococcal meningitis
• Resistance common if used alone

Griseofulvin:

• Disrupts mitotic spindle, binds keratin
• Dermatophyte infections only (accumulates in skin, hair, nails)
• Teratogenic — contraindicated in pregnancy

Terbinafine:

• Inhibits squalene epoxidase
• Dermatophytes, onychomycosis
• Effective, relatively safe

8. Antifungal Resistance

Azole Resistance:

• C. krusei: Intrinsically resistant to fluconazole
• C. glabrata: Dose-dependent susceptibility to fluconazole
• A. fumigatus: Azole-resistant clinical isolates (TR34/L98H mutation)

Echinocandin Resistance:

• FKS mutations in Candida (particularly C. glabrata)
• Rare but increasing

Mechanisms:

• Increased drug efflux pumps
• Target enzyme modification
• Biofilm formation

9. Mycotoxins

Aflatoxin:

• Aspergillus flavus, A. parasiticus
• Contaminates peanuts, corn, cottonseed
• Hepatotoxic, carcinogenic (aflatoxin B1)
• Associated with hepatocellular carcinoma
• Liver damage, acute hepatitis

Ergot Alkaloids:

• Claviceps purpurea (rye)
• Vasoconstriction → ergotism (St. Anthony’s fire)
• Hallucinogenic (lysergic acid diethylamide, LSD)

Trichothecenes:

• Fusarium species
• Alimentary toxic aleukia (fatal)

10. Fungal Immunology

Cell-Mediated Immunity (CMI):

• Primary defense against fungi
• Th1 response: IFN-γ → activates macrophages
• Th2 response: Promotes allergic/IgE responses (ABPA)
• Deficient CMI → disseminated fungal infections

Antibody Responses:

• Limited protective value
• Used for diagnosis (serology)
• IgE in allergic fungal diseases

Diagnostic Tests:

• Skin tests: Delayed-type hypersensitivity (histoplasmin, coccidioidin)
• Serology: Antibody detection (immunodiffusion, complement fixation, ELISA)
• Antigen detection: Histoplasma, Cryptococcus (CRAG), Galactomannan (Aspergillus), β-D-glucan
• Culture: Gold standard but slow
• Molecular: PCR, sequencing

Practice Questions for NEET PG

1. Compare the cell membranes of fungi and humans, and explain the basis for selective antifungal toxicity.
2. Describe the clinical features and diagnosis of Candida infections.
3. Explain the pathogenesis of Histoplasmosis.
4. Discuss the mechanism of action of amphotericin B and its major side effects.
5. Compare and contrast the three endemic dimorphic fungi.

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