Fungi: Forms, Hyphae and Mycelium

Fungi Overview

• Fungi are heterotrophic eukaryotes
• The cell wall is composed of chitin
• The cell membrane contains ergosterol
• Fungi are principally decomposers
• Most fungi undergo alteration of the reproductive cycle
• Fungi secrete digestive enzymes into their environment

Forms of Fungi

• Fleshy fungi are filamentous

Microscopic Fungi

• Yeast is non-filamentous and reproduces through budding
• Saccharomyces cerevisiae is an example of budding yeast
• Some yeast divides evenly and are grouped into Fission Yeast, such as Schizosaccharomyces pombe
• Mold is another form of fungi
• Some fungi, called dimorphic fungi, can be filamentous and non-filamentous, depending on the growth environment

Hyphae

• Mycelium is the body of a fungus and is composed of one or more hyphae
• Septate hyphae with no pore provide complete partition between cells
• Septate hyphae with pores allow flow of organelles and nutrients between cells
• Aseptate hyphae, aka coenocytic, are one long hypha that allow movement of cytosolic content, including the nucleus
• Vegetative hyphae have a rhizoid anchoring structure for nutrient acquisition and growth
• Reproductive hyphae are specialized to carry fungal spores

Fungal Spores

• Fungal spores are true reproductive spores, unlike bacterial endospores
• Spore type is how fungi are usually identified

Asexual Spores

• Asexual spores are produced by an individual fungus through mitosis, without mixing genetic material
• Sporangiospores are enclosed in a sac
• Conidiospores are not enclosed in a sac

Sexual Spores

• Sexual spores are produced by the fusion of nuclei from two different fungi, which results from sexual reproduction between the (+) and (-) strain

Phylum: Zygomycota (Conjugation Fungi)

• Zygomycota are saprophytic molds with coenocytic (aseptate) hyphae
• Asexual spores are sporangiospores
• Sexual spores are zygospores
• Rhizopus stolonifera is a common species that causes rot on strawberries
• Mucor circinelloides can cause fungal nail mycosis, or superficial mycosis, in people who process oranges

Phylum: Ascomycota (Sac Fungi)

• Ascomycota is the largest and most diverse fungal phylum, many of which are medically relevant
• Ascomycota includes mold with porous septate hyphae and some yeast
• Asexual spores are conidiospores
• Sexual spores are ascospores

Special Case: Ergot

• Ergot is a mold that grows on crops like rye, wheat, corn, and barley
• Ergot produces an alkaloid compound called ergotamine, a derivative of lysergic acid
• Consuming ergot causes ergotism
• Symptoms of ergotism include burning sensations in limbs, fever, muscle spasms, hallucinations, paranoia, and mania
• Ergot is suspected to have played a role in prehistoric fertility cults, the Epidemic of St. Vitus' dance, the European & Salem witch trails, and the French Revolution

Phylum: Basidiomycota (Club Fungi)

• Basidiomycota can produce fruiting bodies
• Asexual spores: varies
• Sexual spores: basidiospores
• Amanita muscaria produces muscimol, which causes hallucinogenic effects

Mycosis

• Systemic mycosis affects the bloodstream
• Subcutaneous mycosis affects deep tissue
• Dermatomycosis affects the top or underneath of the skin
• Superficial mycosis is cosmetic and not deadly
• Opportunistic mycosis is normally harmless

True Fungal Pathogens

• Histoplasma
• Blastomyces
• Coccidioides
• Paracoccidioides

Coccidioidomycosis: Valley Fever

• Coccidioidomycosis is caused by Coccidioides immitis, a phylum Ascomycota
• At 37°C, the arthrospores germinate to produce large spherical cells, aka spherules
• Route of entry is the respiratory system
• Primary infection is 60% asymptomatic or 40% cold-like symptoms
• About 5% of individuals develop a disseminated form of coccidioidomycosis

Coccidioidomycosis Complications

• Coccidioidomycosis complication includes fungomas
• It also includes nodular growth in the lung that causes cavity formation in the lung and compromises respiration
• Cutaneous lesions also result, which is local damage to the tissue
• Furthermore, osteomyelitis can occur, where fungal growth occurs in the bone tissue

Common Anti-Fungal Drugs

• Amphotericin B disrupts the plasma membrane and is mainly used for Valley Fever
• It is highly toxic and is only used in the most severe disseminated cases
• It is expensive at greater than $3,000 per month for one year and may not be covered by insurance because of the variability in the efficacy
• Azole drugs interfere with ergosterol synthesis, such as fluconazole, itraconazole, and voriconazole
• Azoles cannot be taken by pregnant women because they can cause deformities in the fetus and other side effects

Antifungal Drugs

• There are six categories of antifungal agents
• Polyenes (amphotericin B) disrupts membrane integrity
• Azoles (imidazoles, triazoles) interfere with ergosterol synthesis
• Allylamines (terbinafine, lamisil) interfere with ergosterol synthesis
• Echinocandins (caspofungin) blocks fungal cell wall synthesis
• Griseofulvin blocks cell division
• Flucytosine inhibits RNA synthesis

Subcutaneous Mycosis: Sporotrichosis

• Sporotrichosis is caused by the agent Sporothrix schenckii, a phylum Ascomycota
• The route of entry is traumatized skin
• It is caused by penetration by thorns, wood, or animal scratches (or bites)
• The fixed form is one lesion without involvement of the lymphatic system
• The lymphocutaneous form involves lymphatic involvement, the appearance of necrotic tissue, liquefaction, or ulceration

Skin Biopsy

• Skin biopsy of an infected cat depicts granulomatous infiltrate with multiple classes of white blood cells, such as macrophages and neutrophils, engulfing cigar shape and round yeast cells
• It is treatable with azole drugs, which interfere with ergosterol synthesis to weaken the cell membrane of fungal cells

Dermatomycosis: Ring Worm (Tinea)

• Dermatomycosis is caused by the agent Trichophyton sp., Microsporum sp., and/or Epidermophyton sp.
• It is phylum Ascomycetes
• The route of entry is direct contact
• Ring worm produces keratinase to destroy keratin in the upper layer of skin to burrow deeper into the epidermal layer to prevent being sloughed off with old skin cells
• Manifestations of Tinea include Tinea capitis (scalp), Tinnea faciei (face), and Tinnea pedis (feet)

Opportunistic Mycosis: Candidiasis

• Candida sp. (yeast) is the dominant opportunistic fungal pathogen and is phylum Ascomycetes
• Candida albicans occurs as normal microbiota
• Candidiasis can be transmitted through surgery, childbirth, and sexual contact, but it is normally not contagious
• C. albicans accounts for about 70% of healthcare-associated fungal infections
• Two common places for Candida sp. infection include the oral cavity that leads to oral candidiasis and the vagina that leads to vulvovaginal candidiasis

Opportunistic/Systemic Mycosis

• Candidiasis is caused by Candida auris
• Candida auris can cause systemic candidiasis that affects the blood stream, CNS, and other organs
• Candida aurisis multi-drug and disinfectant resistant and highly virulent
• Candida auris spreads fastest in long-term care facilities among patients that are severely immunocompromised
• Candida auris is carried on patients' skin without causing infection, which increases its spread

Opportunistic or True Mycosis: Cryptococcosis

• Causative agents are *Cryptococcus gattii *and Cryptococcus neoformans, which are Basidiomycota
• Route of entry is inhalation of basidiospores
• C. gattii is an encapsulated yeast found in decaying trees around the world
• Spreads through dried, contaminated bird feces, specifically pigeons
• Signs and symptoms include a cough, and/or chest pain at first
• It’s then cleared by WBC, and lies dormant, or spreads. ~30% mortality rate.
• C.neoformans typically only affects immunocompromised individuals, but *C. gattii *affects healthy adults.
• Treatment includes amphotericin B or fluconazole, and flucytosine

Pulmonary Cryptococcosis

• This form of the disease affects the lungs and presents as pneumonia; the most common form of the infection

Primary/Secondary Cutaneous Cryptococcosis

• This is a disseminated, systemic form of the disease that causes lesions and nodules.
• Known as, "Pigeon breeder's disease"

Cryptococcal Meningitis

• This form occurs after the pulmonary form when the fungus spreads to the CNS, and causes a swelling of the tissue covering the brain; fungus may spread to other organs

Epizootic Mycoses: Chytridiomycosis

• This is caused by Batrachochytrium dendrobatidis (aka Chytrid fungus)
• The route of entry is skin exposure in water
• It infects the epidermis of frogs and toads
• It prevents them from thermoregulating, breathing, and absorbing water
• It was discovered in 1998, and likely endemic to Africa and Asia
• It’s found on every continent with amphibians and caused massive population declines and extinctions
• Research indicates that frogs can develop immunity to Bd when inoculated with the soil bacterium Janthinobacterium lividium (secretes antifungal compounds)

Epizootic Mycoses: White Nose Syndrome

• Causative agent is Pseudogymnoascus destructans
• Route of entry is skin to skin contact
• It colonizes the epidermis of the muzzle and wings of bats
• Leads to respiratory failure and blood poisoning
• Discovered in 2006 in New York state and currently found in North and South America
• Approximately 5.7 to 6.7 million bat deaths between 2006-2012
• Up to 90% population die off in some areas
• Treatment with Pseudomonas fluorescens as a probiotic which has anti-fungal properties