What are Fungi? What disease they cause?

Fungi and Human Mycoses

• Fungi are eukaryotic cells, with membrane bound organelles, a nucleus, and 18s RNA sequences.
• Their cell membrane contains ergosterol where ours has cholesterol.
• Their cell wall contains complex polysaccharides that stain with PAS (red) and GMS (black).
• It also contains chitin, which helps penetrate host tissues.

Fungus Morphology

Two major morphologic forms:  yeast and hyphae (filamentous).

• Dichotomous hyphae have acute angled forks and septae. They are stiff and narrow like a tree. 
• Dichotomous hyphae often signal Aspergillus.
• Right angled hyphae have square angles and no septae. They are broad and ribbony. Right angled hyphae often signal Zygomycetes.
• Classic Dimorphism is when a fungus is filamentous in the environment, but switches to a yeast form in the body.
• Reverse Dimorphism is the opposite. The fungus is a yeast in the environment, but becomes mixed yeast/filamentous in the body.  If you see mixed yeasts and hyphae, it is Candida.

Note: Yeast with germ tubes are pathognomonic for Candida albicans.

Fungus Structure
1.  Capsule.  The only fungus with a capsule is Cryptococcus.  Capsule protects against host immune response, especially neutrophils.
2.  Cell wall.  Polysaccharides include glucan, mannan, and chitin.  Mannans are more in yeast, chitin in filamentous fungi.  Circulating glucans and mannas are markers of fungal invasion.  The cell wall is not a barrier to the environment!
3.  Cell membrane.  This is the real barrier to the environment.  Remember that fungi use ergosterol where we use cholesterol.

Fungal Reproduction
Most undergo sexual reproduction through sporulation.
A few reproduce asexually, also through sporulation.  Best example are the Zygomycetes.
Spores are not transmitted person to person.  Fungi are normal flora or are encountered in the env.

1.  Zygomycetes reproduce sexually.  Good example of a Zygomycete is Rhizopus.  These fungi often penetrate the nasopharynx of diabetic patients.
2.  Ascomycetes reproduce sexually.  Examples of Ascomycetes include Histoplasma and Dermatophytes.
3.  Basidiomycetes reproduce sexually.  Good example is Cryptococcus neoformans.
4.  Deuteromycetes reproduce asexually.  A good example of Deuteromycetes is Candida.

Factors associated with infection

• Cell surface receptors, hydrolytic enzymes, host mimicry.
• The polysaccharide capsule of Cryptococcus inhibits phagocytosis.

Types of Fungal Infections
1.  Superficial, no inflammation.  Tinea versicolor.

2.  Mucocutaneous, inflammation but non-invasive.  Dermatophytosis, mucocutaneous Candida.
3.  Subcutaneous.  Often following trauma with natural wood or woody plants like roses.
4.  Deep mycoses:
--Opportunistic deep mycoses are PMN-dependent!  These include Candida, Aspergilla, Zygomycetes.
--Pathogenic deep mycoses are CMI-dependent!  This includes Histoplasmosis.

Common Cutaneous and Mucosal Mycoses

Superficial Mycoses

• Fungus is confined to the dead skin and doesn’t illicit inflammation.  Cosmetic problem only.
• Tinea versicolor is a discoloration of the skin caused by the fungus Malassezia furfur.  Under the microscope it appears as “spaghetti and meatballs” with clumps of yeasts and short hyphae.

Cutaneous Mycoses

• Sight: Fungus is confined to the mucosa, skin, hair, and nails, causing minor brisk inflammation.
• Mucosal/Cutaneous Candidiasis is most commonly caused by Candida albicans.  This is an opportunistic infection with T-cell deficiency, such as with AIDS or heavy steroids.
• On mucosal surfaces it causes white plaques made up of both yeast and hyphae.
• On cutaneous surfaces it causes red, scalded lesions in intertriginous areas.

Dermatophytosis 

• Is classically called ringworm, and is the only fungi that is transmitted from 
• person to person.  The various manifestations are all caused by T. rubrum (“ringworm”).
• T. rubrum has long, brancing, septate hyphae.
• Tinea capitis is a ringworm of the scalp occuring only in children.  Often from infected dogs.
• Tinea pedis is ringworm of the feet, also called “athlete’s foot.”
• Tinea unguium is a nail infection with extensive extra keratin production.

Opportunistic Mycoses

• Different opportunistic mycoses occur depending on the type of opportunity:
• Altered T-cell function (AIDS) ?  Mucocutaneous candida, Cryptococcosis, Pneumocystis, Histo
• Altered phagocytic function (neutropenia) ? Candidiasis, Aspergillosis, Zygomycosis

Candida

• These yeasts are part of our normal flora.  The most virulent and common species is Candida albicans.  This is distinguished by the presence of germ tubes on the yeasts.
• Candida in general always has hyphae, pseudohyphae, and yeasts all at once.

Mucocutaneous Candidiasis

• Occurs in immunosuppressed patients, such as those with HIV, on steroids, or pregnant.
• Invasive candidiasis occurs in hospitalized patients, such as those with burns, trauma, catheters, or transplant patients.  This infection with disseminate in the blood and seed organs.
• Candida albicans has hydrolytic activity and host mimicry.  Remember that it has reverse dimorphism, and converts between yeast and pseudohyphae with germ tubes.

Aspergilla

• All Aspergilla infections are opportunistic.  Aspergilla have angular dichotomously branching septate hyphae.
• Invasive Aspergillosis occurs in severely immunosuppressed patients, such as those with neutropenia, bone marrow transplant recipients, on steroids, or in endstage AIDS.
• The spores are inhaled, and invade lung parenchyma with their hyphae.  They can colonize old TB cavities, creating a fungal ball.

Zygomycetes

• Zygomycetes such as Rhizopus have right angle branching non-septate hyphae.
• Invasive Zygomycosis most often seen in diabetics with acidosis!
• Nasocerebral invasion that starts in sinuses and extends to the brain.  Remember it’s in diabetics.

Cryptococcus

• Generally, these opportunistic infections are caused by Cryptococcus neoformans.
• Cryptococci are encapsulated!!  The capsule inhibits phagocytosis.
• Cryptococcosis usually strikes T-cell compromised patients such as AIDS patients.
• It disseminates across the blood-brain barrier and causes meningioencephalitis.

Pneumocystis

• Generally, these opportunistic infections are caused by Pneumocystis carinii.
• It strikes patients with depleted cell mediated immunity, not neutropenic patients.  Generally this means patients with HIV.
• Pneumocystosis is an alveolar-interstitial pneumonia.

Deep Pathogenic Fungi – Histoplasmosis

• Pathogenic fungi can occasionally cause infection in normal hosts.  These fungi include Histoplasmosis, Coccidioides, and Blastomyces.  
• They are encountered in their natural environments, not person to person.  Spores are inhaled, usually causing chronic inflammation and granuloma formation.

Histoplasmosis (Histoplasma capsulatum)

• Spores are inhaled, and usually don’t cause disease.  If inoculum is large or patient is       T-cell compromised (HIV), Histoplasmosis may cause respiratory or even disseminated infection of endothelial cells.
• Histoplasmosis is a dimorphic fungus, being filamentous in nature and yeast in the body.
• Inhaled spores convert to yeast and are phagocytosed by alveolar macrophages but replicate inside macrophage lysosomes.  In a normal host this will normally cause a granuloma, with eventual necrosis, fibrosis, or calcification.  HIV patients do not form granulomas, and the fungus disseminates.

See pharmacology section for drugs related to fungus.