15.1 Fungi

Why fungi are a scored Microbiology topic

/practice/nbce-part1Practice questions with detailed explanations

Quick Answer: Fungi are eukaryotes with chitin-rich walls and ergosterol membranes. Yeasts are unicellular; molds are filamentous hyphae. Thermally dimorphic pathogens are mold in the cold environment and yeast (or spherules) in the warm host. Dermatophytes eat keratin. Candida is normal flora gone opportunistic. Cryptococcus is an inhaled encapsulated yeast. Endemic mycoses are geography-locked inhalation diseases. Aspergillus and Mucorales are molds of the immunocompromised. Pneumocystis is a fungus that ignores ergosterol drugs.

Structure and biochemistry that the exam actually uses

A fungus is a eukaryote. It has a nucleus, 80S ribosomes, mitochondria, and sterol-containing membranes. Those facts separate it from bacteria (70S, peptidoglycan, no sterols except in Mycoplasma) and explain drug targets. The cell wall is chitin, β-glucans, and mannans—not peptidoglycan, so β-lactams do nothing. The plasma membrane contains ergosterol. Polyenes (amphotericin B, nystatin) bind ergosterol and punch pores. Azoles inhibit lanosterol 14-α-demethylase and block ergosterol synthesis. Allylamines (terbinafine) inhibit squalene epoxidase and are the dermatophyte oral/topical workhorse. Echinocandins inhibit β-1,3-glucan synthase in the wall. If a stem says the organism’s membrane uses cholesterol instead of ergosterol, you are looking at Pneumocystis, and the ergosterol drugs fail.

Yeast is a unicellular fungus that divides by budding (blastoconidia) or, less often, fission. On agar it makes creamy colonies. In tissue you see round or oval cells, sometimes with pseudohyphae (Candida) or a capsule (Cryptococcus). Mold (mould) grows as hyphae—tubular filaments. A mass of hyphae is a mycelium. Septate hyphae have cross-walls (Aspergillus, dermatophytes). Aseptate (coenocytic) hyphae lack regular septa and are the Mucorales signature. Asexual spores are conidia (Aspergillus, dermatophytes, dimorphic molds at 25°C) or sporangiospores inside a sac (Rhizopus). Arthroconidia are barrel-shaped fragments of hyphae—the infectious form of Coccidioides in dust.

Dimorphic in the Part I sense almost always means thermally dimorphic: mold at ~25°C (environment, Sabouraud plate left on the bench) and yeast at ~37°C (tissue, or a 37°C plate). Memory line: mold in the cold, yeast in the beast. The named set is Histoplasma capsulatum, Blastomyces dermatitidis, Paracoccidioides brasiliensis / lutzii, Sporothrix schenckii, and Talaromyces (Penicillium) marneffei. Coccidioides immitis / posadasii is thermally dimorphic in lifestyle but the tissue form is a spherule filled with endospores, not a budding yeast—do not call spherules yeasts on a discriminator. Candida albicans is polymorphic (yeast, pseudohyphae, true hyphae) rather than a classic soil-to-yeast dimorph. Cryptococcus is a yeast in tissue and in the lab; its sexual filamentous teleomorph exists in nature but is not the clinical form you name.

Culture is classically on Sabouraud dextrose agar (acid pH near 5.6, which suppresses many bacteria). Dimorphics are proven by growing the mold phase at 25°C and converting to yeast at 37°C—never open a mold plate of a dimorphic on the open bench; arthroconidia of Coccidioides are highly infectious to laboratory staff. KOH (10–20%) dissolves keratin so hyphae and yeasts stand out in skin, hair, and nail scrapings. Calcofluor white binds chitin and fluoresces. Gomori methenamine silver (GMS) and PAS stain fungi in tissue. India ink (or nigrosin) outlines the Cryptococcus capsule as a clear halo; mucicarmine stains that capsule red. Cryptococcal antigen (lateral flow or latex) has largely replaced India ink in real labs, but the halo remains an exam image.

Pathogenicity, immunity, and resistance

Fungi do not make classic AB exotoxins the way Corynebacterium does. Pathogenicity is adhesion, morphologic switching, immune evasion, and, for a few, mycotoxins.

Neutrophils are the main defense against Candida in blood and against Aspergillus hyphae. Neutropenic patients (chemotherapy, marrow failure) get invasive filamentous disease. T-cell / macrophage immunity (Th1, IFN-γ, granulomas) contains Cryptococcus, Histoplasma, Coccidioides, and Pneumocystis. AIDS, TNF inhibitors, and high-dose steroids open those doors. Antibody is not the primary clearance mechanism for most deep fungi, which is why hypogammaglobulinemia is the wrong host defect on a crypto-meningitis stem. Host defects are taught with immunology (/study-guides/nbce-part1/microbiology-host-pathogens/immunology); here you pair the defect with the fungus.

Resistance in fungi is not plasmid β-lactamase. Azole resistance in Candida krusei (intrinsic), C. glabrata (often acquired), and C. auris (often multidrug) is an efflux-and-target story. C. auris also persists on plastic and in ICUs and has been nationally notifiable in the United States since 2019—an epidemiology crossover for the third section of this chapter. Polyene resistance is uncommon because ergosterol is hard to abandon; Pneumocystis simply never used it.

Dermatophytes: keratin, tinea, and fomites

Dermatophytes are molds that infect keratinized tissue only: stratum corneum, hair, nail. They do not invade living dermis in immunocompetent hosts. Three genera:

Clinical names are anatomic, not genus names: tinea corporis (body, ring with active border), tinea cruris (groin), tinea pedis (athlete’s foot), tinea capitis (scalp; kerion is an inflammatory boggy plaque), tinea unguium / onychomycosis (nails), tinea barbae (beard). Tinea versicolor is not a dermatophyte: it is Malassezia furfur, a lipophilic yeast of sebum-rich skin, with spaghetti-and-meatballs yeast and short hyphae on KOH, and hypopigmented or hyperpigmented macules that fail to tan.

Reservoirs and transmission. Anthropophilic species (T. rubrum, T. tonsurans, E. floccosum) spread person to person and by fomites—locker-room floors, shared towels, wrestling mats, poorly cleaned treatment-table face paper if a patient has tinea faciei. Zoophilic species (M. canis) come from cats and dogs and tend to inflame more. Geophilic species (Nannizzia gypsea, formerly Microsporum gypseum) come from soil. Spores survive in shed scale for months. Person-to-person spread of dermatophytes is real; person-to-person spread of Histoplasma is not.

Wood lamp: Microsporum ectothrix fluoresces; T. tonsurans endothrix does not—so a dark lamp does not rule out tinea capitis in U.S. schoolchildren. Confirm with KOH or culture. Terbinafine or griseofulvin (hair) are treatment facts you may see as distractors; the organism ID is the Part I job.

Candida: flora, germ tubes, and opportunism

Candida albicans is the prototype. It lives as normal flora of the mouth, gut, and female genital tract. Disease is overgrowth or invasion, not a newly acquired zoonosis. Triggers: broad-spectrum antibiotics (kill competing bacteria), diabetes (glucose), pregnancy and oral contraceptives, inhaled or systemic steroids, dentures, moisture (diaper, skin folds), neutropenia, and central lines.

Morphology. Yeast and pseudohyphae in tissue are the teaching pair; true hyphae occur in invasion. A germ-tube test (hyphal outgrowth in serum at 37°C in 2–3 hours) historically identified C. albicans (and C. dubliniensis). C. glabrata stays yeast-only and is more azole-resistant. C. krusei is intrinsically fluconazole-resistant. C. auris is the emerging, often multidrug-resistant hospital yeast that colonizes skin and survives on surfaces.

Syndromes. Oral thrush: white plaques that scrape off (unlike hairy leukoplakia). Candida esophagitis: odynophagia in AIDS, typically at CD4 counts <100 cells/µL. Vulvovaginitis: thick discharge, normal pH (unlike Trichomonas or bacterial vaginosis). Diaper and intertrigo. Chronic mucocutaneous candidiasis: T-cell defects (AIRE, STAT1). Catheter candidemia and right-sided endocarditis in injection-drug use. Hepatocellular microabscesses after neutrophil recovery in leukemia. Neutropenic dissemination is a neutrophil story; mucosal overgrowth is a local flora story.

Transmission of thrush is not a classic airborne epidemic. Neonates can acquire it from the birth canal. Hands and fomites matter for C. auris in hospitals. For C. albicans in a healthy adult, the reservoir is usually the patient’s own gut or mucosa.

Cryptococcus: capsule, pigeons, meningitis

Cryptococcus neoformans is a narrow-based budding yeast with a polysaccharide capsule. Reservoir: soil enriched with pigeon droppings (and other bird guano), worldwide. Transmission: inhalation of desiccated yeast. Not person-to-person. Pulmonary infection may be silent; the feared disease is meningitis / meningoencephalitis in AIDS or other T-cell failure—subacute headache, cranial neuropathies, gelatinous soap-bubble cysts in the basal ganglia. India ink on CSF shows halos; cryptococcal antigen on CSF or serum is more sensitive; mucicarmine stains the capsule in tissue. Opening pressure is often high; India ink can be negative when the burden is low—antigen still wins.

Cryptococcus gattii is associated with eucalyptus and soil trees, can infect immunocompetent hosts, and has a Pacific Northwest and tropical footprint. Capsule and meningitis logic is the same; the host and geography differ.

A chiropractic-relevant presentation is suboccipital or global headache in a patient with known HIV or unexplained weight loss. That is not a cervical-adjustment problem until meningitis is excluded. Immunology of AIDS is in /study-guides/nbce-part1/pathology-mechanisms/immune-disorders; here you name the encapsulated yeast and the pigeon reservoir.

Endemic (systemic) mycoses

These are dimorphic soil fungi of defined geography. Healthy people inhale a small inoculum, make a granuloma, and often never know. Large inocula or broken T-cell immunity produce pneumonia and dissemination. They are not transmissible person to person—a patient with pulmonary histoplasmosis is not isolated as if they had tuberculosis. (Tuberculosis isolation is an airborne-precaution decision in the epidemiology section; the fungus does not spread that way.)

Histoplasma is the small one inside macrophages—do not confuse it with Leishmania (kinetoplast) or Trypanosoma cruzi amastigotes (also kinetoplast, different geography and vector). Blastomyces is the broad-based bud—same size class as some Coccidioides endospores, but Blastomyces buds; spherules do not bud. Coccidioides arthroconidia are so infectious that a laboratory mold plate is a biosafety event. Climate and dust have expanded the recognized range of Valley fever north and east of the classic desert map; the exam still uses San Joaquin / Arizona as the stem geography.

Sporothrix schenckii is thermally dimorphic but not a pulmonary endemic mycosis. Reservoir: soil and plant matter. Transmission: traumatic inoculation—rose thorns, sphagnum moss, splinters (rose-gardener disease). Clinical: lymphocutaneous ascending nodules along lymphatics of the arm. Tissue: cigar-shaped 2–6 µm yeasts (often scarce). At 25°C, daisy-like conidia on a conidiophore. Asteroid bodies (Splendore–Hoeppli) may appear. Rare pulmonary disease follows inhalation in alcoholics. This is a skin-and-lymphatic inoculation cycle, not an Ohio-river inhalation cycle.

Aspergillus and the Mucorales contrast

Aspergillus fumigatus is the usual invasive species; A. flavus is the aflatoxin species and a sinus/skin player; A. niger may colonize cavities. Morphology in tissue: septate hyphae with acute-angle (~45°) dichotomous branching. Reservoir: air, dust, construction, compost—inhalation of conidia. Not person-to-person.

Mucorales (Rhizopus, Mucor, Lichtheimia): aseptate (or pauci-septate) ribbon-like hyphae branching at ~90°. Reservoir: bread, fruit, soil; spores inhaled or inoculated. Host: diabetic ketoacidosis (Rhizopus uses ketoreductase; iron is more available), deferoxamine therapy (iron siderophore), neutropenia. Clinical: rhino-orbital-cerebral disease with black necrotic eschar on the palate or turbinates, cranial-nerve palsies, cavernous-sinus invasion. Treatment logic on a basic-science exam is surgical debridement plus amphotericin, not an azole that Aspergillus might get. Branching angle plus host (neutropenia vs DKA) is the highest-yield mold discriminator on Part I.

Pneumocystis jirovecii

Once misclassified as a protozoan, Pneumocystis jirovecii (human; P. carinii is the rat organism) is a fungus. It cannot be cultured on routine fungal media. Membrane sterol is cholesterol, so amphotericin and azoles fail. First-line treatment and prophylaxis: trimethoprim-sulfamethoxazole. Disease: Pneumocystis pneumonia (PCP) when CD4 counts fall below about 200 cells/µL—gradual dyspnea, dry cough, hypoxia, ground-glass interstitial infiltrates, elevated LDH, few physical findings relative to the radiograph. Diagnosis: silver stain of cysts in induced sputum or BAL (cup-shaped cysts, trophozoites on Giemsa). Transmission: airborne person-to-person is now accepted (unlike Histoplasma); serology shows most children have met the organism. Disease in AIDS is usually reactivation or new acquisition in a deficient host, not a soil dimorph. Prophylaxis at CD4 <200 is a prevention fact that belongs equally in epidemiology.

Transmission map you should be able to recite

Fungal vertebral osteomyelitis is uncommon but real in injection-drug use (Candida) and in prolonged neutropenia (Aspergillus). It is a Session 2 micro-plus-pathology crossover, not a primary disc herniation. Most fungal items on Part I are still the table rows above: tissue form, geography, host defect, stain.

Fungi are 15% of the Microbiology domain. Parasites occupy the next 15% and use life cycles the way fungi use tissue forms.