5.3 Fungi

Introduction to Fungi

Relevance of fungi in microbiology

Fungi are eukaryotic microorganisms that show up across medicine, industry, and ecology. They come in two basic forms:

• Yeasts are unicellular fungi
  • Reproduce by budding or fission, leading to rapid population growth
  • Used in fermentation to produce bread, beer, and wine
  • Some yeasts, such as Candida albicans, are opportunistic pathogens that cause infections in immunocompromised hosts
• Molds are multicellular fungi
  • Grow as filamentous hyphae that form an interconnected network called a mycelium
  • Produce spores for reproduction and dispersal
  • Some molds, like Penicillium, produce antibiotics, while others, such as Aspergillus oryzae, are used in food production (e.g., soy sauce fermentation)

Distinguishing characteristics of fungi

What separates fungi from bacteria, plants, and protists? A few key traits:

• Eukaryotic organisms with membrane-bound organelles and a true nucleus (unlike prokaryotic bacteria)
• Cell walls made of chitin, a tough polysaccharide. This is different from peptidoglycan in bacteria and cellulose in plants.
• Heterotrophs that obtain nutrients by absorption from their environment. They secrete enzymes externally to break down organic material, then absorb the resulting small molecules.
• No chlorophyll, so they cannot photosynthesize (unlike plants and algae)
• Reproduce by producing spores, both sexually and asexually
• Some fungi exhibit dimorphism, meaning they can switch between yeast and mold forms depending on environmental conditions (especially temperature). This is clinically significant because several human pathogens are dimorphic.

Fungal Reproduction and Classification

Asexual vs. sexual fungal reproduction

Fungi can reproduce both asexually and sexually. Many species default to asexual reproduction when conditions are favorable and switch to sexual reproduction under stress.

Asexual reproduction produces genetically identical offspring (clones) from a single parent:

1. Fragmentation occurs when hyphae break into smaller pieces, each capable of growing into a new mycelium
2. Budding involves a small outgrowth forming on the parent cell, which pinches off and matures into a new individual (common in yeasts)
3. Spore formation occurs when specialized structures produce and release asexual spores, such as conidia (produced at the tips of conidiophores, exposed to air) or sporangiospores (produced inside an enclosed sac called a sporangium)

Sexual reproduction increases genetic diversity through recombination:

1. Two compatible haploid cells (or hyphae) fuse in a process called plasmogamy, bringing two nuclei together in one cell
2. The nuclei eventually fuse (karyogamy) to form a diploid zygote
3. Meiosis produces haploid spores, which germinate into new haploid individuals

The type of sexual spore produced is a major basis for classifying fungi into phyla.

Major groups of fungi

• Zygomycota
  • Produce thick-walled zygospores during sexual reproduction, formed by the fusion of two compatible hyphae
  • Hyphae are typically coenocytic (lacking septa/cross-walls)
  • Example: Rhizopus stolonifer (common bread mold)
• Ascomycota (the "sac fungi")
  • Produce ascospores within sac-like structures called asci (singular: ascus)
  • The largest fungal phylum, with enormous diversity
  • Examples: Saccharomyces cerevisiae (baker's/brewer's yeast), Penicillium chrysogenum (produces penicillin)
• Basidiomycota (the "club fungi")
  • Produce basidiospores on club-shaped structures called basidia
  • Includes most familiar mushrooms and some important pathogens
  • Examples: Agaricus bisporus (button mushroom), Cryptococcus neoformans (pathogenic yeast causing meningitis)
• Deuteromycota (Fungi Imperfecti)
  • A classification for fungi with no known or observed sexual stage
  • Not a true phylogenetic group. As molecular techniques reveal sexual stages, species get reclassified into one of the other phyla.
  • Examples: Aspergillus species, Trichophyton rubrum (causes athlete's foot)

Classification system for fungi

Classification relies on a combination of morphological characteristics (hyphal structure, spore type), reproductive structures, and increasingly, molecular sequence data. The four traditional phyla are:

1. Phylum Zygomycota
2. Phylum Ascomycota
3. Phylum Basidiomycota
4. Phylum Deuteromycota (Fungi Imperfecti)

Fungal Pathogens and Toxins

Common fungal pathogens and infections

Fungal infections (mycoses) range from superficial skin conditions to life-threatening systemic diseases. Immunocompromised individuals are at the greatest risk for severe mycoses.

• Candida albicans
  • Causes candidiasis, including oral thrush and vaginal yeast infections
  • Normally part of the human microbiota but becomes pathogenic when the immune system is weakened or normal flora is disrupted (e.g., after antibiotic use)
• Aspergillus fumigatus
  • Causes aspergillosis, ranging from allergic reactions to invasive lung infections
  • Spores are inhaled from the environment; invasive disease occurs primarily in immunocompromised patients (transplant recipients, chemotherapy patients)
• Trichophyton and Microsporum
  • Cause dermatophytoses (ringworm, athlete's foot, jock itch)
  • These dermatophytes infect keratinized tissues: skin, hair, and nails. Despite the name "ringworm," no worm is involved.
• Cryptococcus neoformans
  • Causes cryptococcosis, a potentially fatal meningitis
  • Infection begins with inhalation of spores (often from pigeon droppings), which can disseminate to the central nervous system, especially in AIDS patients

Toxin-producing fungi and health impacts

Some fungi produce mycotoxins, secondary metabolites that cause acute or chronic toxicity in humans and animals. These toxins contaminate food supplies rather than causing direct infection.

• Aflatoxins, produced by Aspergillus flavus and A. parasiticus, contaminate crops like corn, peanuts, and tree nuts. They are among the most potent known carcinogens and are strongly linked to liver cancer.
• Ergot alkaloids, produced by Claviceps purpurea, contaminate rye and other cereals. Ergotism causes hallucinations, gangrene, and convulsions. Historically, ergot poisoning may have contributed to events like the Salem witch trials.
• Ochratoxins, produced by certain Aspergillus and Penicillium species, contaminate grains, coffee, and wine. They are nephrotoxic (damaging to the kidneys) and potentially carcinogenic.

Proper food storage, crop monitoring, and handling practices are essential to minimize mycotoxin exposure.

Fungal Ecology and Interactions

Ecological roles of fungi

Fungi are among the most important decomposers on Earth. Without them, dead organic matter (especially lignin in wood) would accumulate and nutrient cycling would stall.

Beyond decomposition, fungi form critical symbiotic relationships:

• Mycorrhizae are associations between fungi and plant roots. The fungus extends the root's effective surface area, improving water and mineral absorption (especially phosphorus), while the plant provides the fungus with sugars. Over 80% of land plants form mycorrhizal associations.
• Lichens are partnerships between a fungus and a photosynthetic organism (green algae or cyanobacteria). The fungus provides structure and protection; the photosynthetic partner provides organic carbon. Lichens colonize bare rock and other harsh environments where neither partner could survive alone.

Fungi occupy diverse niches in terrestrial and aquatic environments, playing roles as decomposers, mutualists, parasites, and predators (some fungi even trap nematodes).

Fungal cell structure and antifungal agents

Treating fungal infections is challenging because fungi are eukaryotes, just like human cells. Antifungal drugs must target features unique to fungi while sparing the host.

Two key structural differences are exploited:

• Cell wall: Fungal cell walls contain chitin and glucans, which human cells lack entirely
  • Echinocandins (e.g., caspofungin) inhibit glucan synthesis, disrupting cell wall integrity
• Cell membrane: Fungal membranes contain ergosterol instead of the cholesterol found in human cell membranes
  • Azoles (e.g., fluconazole) inhibit ergosterol synthesis, weakening the membrane
  • Polyenes (e.g., amphotericin B) bind directly to ergosterol, creating pores in the membrane that cause cell contents to leak out

Because of the similarities between fungal and human cells, antifungal drugs tend to have more side effects than antibacterial drugs. This is an important clinical consideration.