Fungal Structure and Basic Biology

Fungi are eukaryotic organisms, sharing far more structural similarity with human cells than bacteria do (see Prokaryotes Versus Eukaryotes). This structural closeness is the reason antifungal drugs have a narrower selective target and generally higher host toxicity than antibacterials.

• Unicellular fungi.
• Reproduce by budding: an outgrowth forms on the parent cell, enlarges, and eventually separates as a daughter cell.
• Some yeast species form pseudohyphae: chains of elongated budding cells that fail to fully separate, resembling but distinct from true hyphae (seen with Candida species, relevant to identifying invasive candidiasis on histology).

• Multicellular fungi.
• Grow as branching filaments called hyphae; a mass of interwoven hyphae forms the mycelium, the visible fungal colony.
• Septate hyphae: divided into individual cells by internal cross-walls (septa), each typically containing one or more nuclei (e.g. Aspergillus).
• Nonseptate (coenocytic) hyphae: no cross-walls, forming a single continuous multinucleate cytoplasm (e.g. the Mucorales, the organisms causing mucormycosis).
• This septate/nonseptate distinction is a direct histological clue used to differentiate invasive mould infections on tissue biopsy.

• A group of fungi that switch morphological form depending on temperature (and, in practice, on whether they are in the environment or in host tissue).
• At environmental temperature (~25°C), grow as mould (hyphal form).
• At body temperature (37°C, inside a host), grow as yeast (or a yeast-like spherule form).
• This temperature-dependent switch is the basis of their pathogenicity and a frequently tested concept. Examples: Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides brasiliensis, Sporothrix schenckii (organism-specific detail covered in Mycology).

Cell wall:

• Chitin: a rigid polymer of N-acetylglucosamine, providing structural strength, absent in human cells, a potential antifungal target (echinocandins target a related wall polymer, beta-glucan, rather than chitin directly, but the wall as a whole is the shared theme).
• Glucans: polysaccharide polymers (beta-1,3-glucan and beta-1,6-glucan) forming a major structural component of the wall; beta-1,3-glucan is the direct target of the echinocandin antifungal class.
• Mannans: mannose-containing polysaccharides on the outer wall surface, contribute to antigenicity and are used in some fungal antigen detection assays (e.g. Aspergillus galactomannan testing).

Cell membrane:

• Contains ergosterol in place of the cholesterol found in human cell membranes. This single difference is the basis of the two major antifungal drug classes: azoles (inhibit ergosterol synthesis) and polyenes, for example amphotericin B (bind ergosterol directly, disrupting membrane integrity). Because amphotericin B has some affinity for human cholesterol as well as fungal ergosterol, this cross-reactivity underlies its characteristic nephrotoxicity.

• Sexual spores: produced by fusion of compatible mating types followed by meiosis, generating genetic recombination. Types (ascospores, basidiospores, zygospores) are used in fungal taxonomy, covered further in Mycology.
• Asexual spores: produced by mitosis without genetic recombination, the more common and clinically relevant reproductive route for most pathogenic fungi, allows rapid dissemination.
• Conidia: the general term for asexual spores produced by moulds, typically formed at the tips of specialised hyphal structures (conidiophores). Conidia are usually the infectious/inhaled form responsible for environmental exposure (e.g. Aspergillus conidia inhaled from the air, germinating into invasive hyphae in a susceptible host).