Fungi differ from bacteria in their cell wall composition: fungal walls contain chitin and glucans, whereas bacterial walls contain peptidoglycan. Fungal cell membranes contain ergosterol as the principal sterol, which serves as the target for many antifungal drugs. Morphologically, yeasts are unicellular and reproduce by budding, while molds are multicellular and form branching filaments called hyphae. Dimorphism is the ability of certain fungi, such as Histoplasma, Blastomyces, and Coccidioides, to switch between yeast and mold forms depending on environmental temperature, growing as molds at room temperature and as yeasts at body temperature. Asexual reproductive spores called conidia form at the tips of specialized hyphae and are useful for laboratory identification.
Major pathogenic fungi include Candida albicans, part of normal flora that causes opportunistic infections such as thrush and vaginal candidiasis, and Cryptococcus neoformans, an encapsulated yeast causing cryptococcal meningitis, especially in HIV/AIDS patients, with the capsule visualized using India ink stain. Histoplasma capsulatum, found in soil enriched with bird or bat droppings in the Ohio and Mississippi river valleys, causes histoplasmosis. Coccidioides immitis, endemic to the southwestern US deserts, causes Valley fever (coccidioidomycosis). Blastomyces dermatitidis causes blastomycosis in the Great Lakes and Mississippi/Ohio river valleys. Aspergillus species produce septate hyphae with acute-angle branching and cause invasive pulmonary infections in immunocompromised hosts, while Aspergillus flavus produces aflatoxins that contaminate food and increase hepatocellular carcinoma risk. Mucor and Rhizopus species (Mucorales) cause mucormycosis with broad, non-septate hyphae branching at wide angles, classically in patients with diabetic ketoacidosis. Pneumocystis jirovecii causes Pneumocystis pneumonia, a classic AIDS-defining illness. Dermatophytes such as Trichophyton, Microsporum, and Epidermophyton infect keratinized tissue, causing tinea (ringworm) infections of skin, hair, and nails.
Antifungal drugs target the unique features of fungal cells. Azoles such as fluconazole inhibit lanosterol 14-alpha-demethylase, blocking ergosterol synthesis and disrupting the fungal membrane. Amphotericin B binds ergosterol directly, forming membrane pores that cause leakage of cell contents. Echinocandins like caspofungin inhibit beta-(1,3)-D-glucan synthase, blocking fungal cell wall synthesis. Griseofulvin disrupts microtubule function and mitosis, making it useful for dermatophyte infections.
Among protozoan parasites, Plasmodium species such as P. falciparum and P. vivax cause malaria, transmitted by female Anopheles mosquitoes; P. falciparum produces the most severe and deadly form. Toxoplasma gondii causes toxoplasmosis, acquired from cat feces or undercooked meat, and is dangerous in pregnancy (causing congenital toxoplasmosis) and in immunocompromised patients. Trypanosoma brucei causes African sleeping sickness via the tsetse fly, while Trypanosoma cruzi causes Chagas disease via triatomine (kissing) bugs. Entamoeba histolytica causes amoebic dysentery and liver abscesses. Giardia lamblia (intestinalis) causes foul-smelling, greasy diarrhea and is transmitted via contaminated water, often affecting hikers. Trichomonas vaginalis is a sexually transmitted protozoan causing vaginitis. Cryptosporidium parvum causes waterborne diarrhea, particularly in immunocompromised patients. Leishmania species cause visceral and cutaneous leishmaniasis, transmitted by sandflies.
Helminthic (worm) infections remain widespread. Trichinella spiralis, acquired from undercooked pork, causes trichinosis. Enterobius vermicularis (pinworm) is the most common helminthic infection in the United States, especially in children. Ascaris lumbricoides, one of the most common helminthic infections worldwide, is acquired via fecal-oral ingestion of eggs. Necator americanus and Ancylostoma duodenale are hookworms that infect humans through skin penetration from contaminated soil. The pork tapeworm Taenia solium can cause cysticercosis when its eggs are ingested, while Taenia saginata is acquired from undercooked beef.