Lecture 9: Fungi

What is mycology?

study of fungi

What is mycosis (mycoses)?

fungal infections

How many estimated species of fungi?

2.2-3.8 million

How many species associated with human disease?

200-300 species

Which species are the major contributors to human disease?

-candida

-aspergillus

-cryptococcus

-histoplasma

-blastomyces

-coccidioides

-mucorales fungi

What are the three major forms of fungi?

1. Filamentous fungi (molds)

2. Yeasts

3. Mushrooms

What are the characteristics of filamentous fungi?

-multinucleate, thread-like hyphae

-septate or non-septate forms

-longitudinal growth and branching

What are the characteristics of Yeast?

-unicellular organisms

-round or oval morphology

-reproduction by budding

What are some commercial importance?

-baking

-brewing

-pharmaceutical production

-antibiotic synthesis

What are fungi relationships with humans?

-normal microbiota of the skin, oral cavity, GI tract, and vagina

-superficial infections of skin, hair, and nails

-opportunistic infections in immunocompromised hosts

-allergic reactions to fungal spores and molds

What are the three types of forms that fungi take?

1. Yeast

2. Mold

3. Dimorphic fungus

Yeast:

unicellular fungus

Ex: Candida albicans, Cryptococcus neoformans

Mold:

multicellular filamentous fungus

Ex: Aspergillus fumigatus, Rhizopus arrhizus

Dimorphic Fungus:

mold in the environment; yeast (or yeast like form) in human tissue

Ex: Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides spp.

What are the characteristics of fungi structure?

-rigid cell wall (made of chitin, glucans, mannans)

-Cytoplasmic membrane (composed of ergosterol + zymosterol)

->ergosterol provides important antifungal drug target

->structure differs sig. from bacterial and human cells

-Hyphae: filamentous growth units of molds

->may be septate with cross walls or aseptate/coenocytic

->interwoven hyphae form a Mycelium

->fungal body: Thallus

Asexual reproduction:

-one parent; no gametes involved

-produces genetically identical offspring

-fast multiplication and spread

-methods: budding, fragmentation, conidia/spore formation

Ex: Aspergilus fumigatus, Histoplasma capsulatum, Cryptococcus neoformans

Sexual reproduction:

-fusion of compatible hyphae or mating types

-generates genetic variation

-Steps: Plasmogamy, Karyogamy, Meiosis

-Produces sexual spores (ascospores, basidospores, zygospores_

Ex: Candida albicans, Aspergillus fumigatus, Rhizopus arrhizus

What are some host defenses?

-low skin pH restricts fungal growth

-fatty acids inhibit colonization

-rapid epithelial turnover removes organisms

-mucosal IgA and IgG limit growth and spread

-IgE (activates mast cells, basophils, eosinophils) and is involved in hypersensitivity response (allergies)

What conditions are favorable to fungal infections?

-disruption of the body's physical, chemical, and physiologic barriers

-loss of cell-mediated immunity

-Immunosuppression (loss of CD4 T1 helper responses)

--opportunistic infections by normal flora (candida albicans)

--increased susceptibility to environmental fungi (aspergillus)

-Disruption of normal bacterial flora

-use of antibacterial drugs

Superficial mycoses:

involve keratinized outermost layers of Skin, hair, and nails

Cutaneous mycoses:

involved the keratin-containing epidermis and deeper layers of hair, skin, and nails

Subcutaneous mycoses:

involve dermis, subq tissue, muscles, and fascia (connective tissue)

Systemic mycoses:

originate in lungs and disseminate to other organs (esp in immunocompromised pt)

Who are some people more at risk for fungal infections?

-cancer patients on immunosuppressive drugs

-virus (HIV) infected individuals

Candida albican:

-yeast

-most common genital fungal infection

-not true STI (sexual transmission can still occur)

Symptoms: itching, burning, redness, white discharge

First line treatment: Fluconazole, Clotrimazole, Miconazole

Candida albicans

thrush, vagnitis

Aspergillus

lung infection, neutropenia

Cryptococcus neoformans

meningitis in AIDS

Histoplasma capsulatum

Ohio/Mississippi River valleys

Coccidioides immitis

Southwestern US

Pneumocystis jirovecii

AIDS pneumonia

Trichophyton

Dermatophyte infections

Malassezia furfur

tinea versicolor

Tinea pedis

"foot fungus" Athlete's foot

Tinea capitis

"Scalp fungus" Scalp ringworm

Tinea cruris

"Groin fungus" Jock itch

Tinea corporis

"Body Fungus" Ringworm on skin

Tinea versicolor

"Color-changing skin fungus"

What is the fungus name of tinea pedis?

trichophyton rubrum (and others)

What is the fungus name of tinea capitis?

Microsporum or Trichophyton species

What is the fungus name of tinea cruris?

Epidermophyton floccosum (and others)

What is the fungus name of tinea corporis?

Trichophyton rubrum (and others)

What is the fungus name of tinea versicolor?

Malassezia furfur: Superficial

Paracoccidioidomycosis brasilensis:

Causative agent: paracoccidioidomycosis brasilensis

Disease: paracoccidioidomycosis

Classification: systemic mycosis

Environmental form: thermally dimorphic fungus

-mold in soil

-yeat in tissues

Disease spectrum:

-asymptomatic infection

-positive skin test

-subclinical infection

-symptomatic infection

-chronic infection

Clinical forms:

-primary pulmonary disease

-acute pulmonary disease

-chronic pulmonary disease

-disseminated disease

Disseminated infection:

-reticuloendothelial system involvement

-skin involvment

-mucous membrane involvment

Candida:

Form: yeast (most common opportunistic mycosis)

Normal flora: skin, mouth, vagina, stool

Major species: albicans, tropicalis, glabrata, parapsilosis, krusei, lusitaniae

Virulence factors: tissue adherence, secretory aspartyl proteases, phospholipases

Immune response: cell wall glycans, monocyte activation, adaptive immunity

Transmission: catheters, prosthetic devices, direct transfer (neonatal oral candidiasis)

Disseminated candidiasis: hematogenous spread, primary infection focus in the blood stream

Cryptocossus:

Form: encapsulated yeast (>50 subspecies)

Main pathogen: Cryptococcus neoformans

Major disease: Meningoencephalitis, subacute or chronic course

Virulence factors: polysaccharide capsule, phenol oxidase, melanizing enzymes

Transmission: inhalation of yeast form

Possible organ involvement: Lungs, skin eyes, prostate, urinary tract, myocardium, bones, joints

Host defense: NK cells, antibody mediate responses, adaptive immunity

High Risk: HIV/AIDS, immunocompromised pt's

Aspergillus:

Major species: Fumigatus

Disease: Aspergillosis, allergic bronchopulmonary aspergillosis (severe allergic reaction)

Host Defense: Macrophages, Neutrophils, Fungicidal mediators

Pulmonary complications: aspergilloma (fungal/mycelial ball), lung cavity formation, hemoptysis

Invasive aspergillosis: immunocompromised pts, blood vessel invasion, multi-organ dissemination

Immune-mediated disease: Th2 dominant responses, Fungal antigen allergy

Mycotoxins: Aflatoxins (A. flavus, A parasiticus), Severe liver damage

Mucor:

Form: Filamentous fungus

Environmental reservoirs: soil, plants, decaying fruits

Common species: circinelloides, hiemalis, indicus, racemosus

Disease: Zygomycosis (Mucormycosis)

Clinical forms:

-Mucocutaneous infection

-Rhinocerebral infection

-pulmonary infection

-renal infection

-gastritis

-septic arthritis

-dialysis associated peritonitis

Pathogenesis: Vascular invasion, tissue necrosis, perineural invasion

Morphology: Hyphae, sporangiophores, sporangia, spores

Pneumocystis:

Causative agent: pneumocystis jiroveci (formerly p. carinii)

Classification: opportunistic fungus (originally classified as a protozoan)

High Risk Groups: HIV/AIDs, premature infants, elderly individuals, immunocompromised pt's

Primary site: lung tissue

Pathogenesis: Alveolar fluid accumulation, impaired oxygen/gas exchange

Clinical significance: Pneumocystis pneumonia, major opportunistic infection

Exam Pearl: AIDs-defining infection, fungal pathogen causing severe pneumonia

Ringworm (Tinea):

Form: filamentous mold infection

Species: Trichophyton, Microsporum, Epidermophyton

Treatment: Terbinafine (topical for skin, oral for scalp/nails)

Transmission: direct skin contact with infected people or animals, sharing personal items, contact with surface found in moist areas (shower stalls, pool areas, etc)

Histoplasmosis:

Disease: pulmonary fungal infection

Causative agent: Histoplasma capsulatum (acquired by inhalation of spores)

Treatment: Traconazole, amphotericin B

Methods of fungal diagnosis?

1. Direct microscopy

2. Culture

3. DNA probes/molecular testing

4. Serology/antigen-antibody testing

Direct Microscopy:

-patient specimen

-microscopic examination

-fungal morphology: yeast, hyphae, pseudohyphae, spores

Culture:

-Specimen inoculation on fungal culture media

-growth and isolation or organism

-indentification of fungal species

DNA probes/Molecular testing:

-rapid organism identification

-detection of systemic fungi

-culture based or molecular confirmation

Serology/Antigen-antibody testing:

-detection of fungal antibodies or antigens

-useful for systemic mycoses

-Ex: Cryptococcus neoformans testing in CSF

Fungi Characteristics:

-Eukaryotic

-Cell membrane sterol: ergosterol

-Ergosterol: unique to fungal cell membranes

Fungal cell wall:

-chitin, glucans, mannans, proteins

-provides structure and protection

-different from bacterial cell walls

Fungal Spores: contribute to hypersensitivity reactions

Antifungal drug targtets:

-Ergosterol synthesis and function

-fungal cell wall (B-glucan) synthesis/metabolism

Mycotoxins:

Aflatoxins: group of related mycotoxins

Aflatoxin B1: produced by aspergillus flavus (common on peanuts)

-aromatic amine derivative

-highly potent dietary carcinogen

-mutagenic effects on hepatocytes (liver cells)

-severe liver damage adn hepatotoxicity