Introduction To Fungi

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Normal flora on humans

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Candida
(few fungi are normal flora to humans)

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Candidiasis and tinea versicolor

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only two fungi that do not originate from exogenous source

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Fungi Kingdom

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2 phylum
1 form-class

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Phylum Zygomycota

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produce zygote during sexual cycle
includes zygomycosis

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Phylum Dikaryomycota

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2 nuclei in same protoplasm for extended periods of time following sexual conjugation
includes:
ringworm, histoplasmosis, blastomycosis, cryptococcosis

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Form class: Deuteromycotina

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Fungi imperfecti: no sexual stage known
includes: candidiasis, tinea fungi, coddidioides

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Produce sterols in plasma membrane

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no cholesteral
fungi have ergosterol

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Cell wall

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composed of chitin
a homopolymer of Beta-(1,4)-N-acetylglucosamine

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Some fungi produce a capsule

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only one encapsulated fungus as of now that produces disease in humans= Cryptococcus neoformans

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Fungal infections

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slow to develop and chronic
due to slow division time

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Fungal gram stain

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most fungi stain Gram positive

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Two basic morphological forms

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yeasts and hyphae

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Yeasts

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unicellular
reproduce asexually by budding or fission

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Hyphae

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multicellular fungi
reproduce asexually and/or sexually

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Most fungi occur in hyphal form as branching, threadlike tubular filaments

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filamentous structures either lack cross walls, called coenocytic, or have cross walls, called septate

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mycelium

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mass of hyphal elements
aka mold

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conidia

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spores
produced by aerial hyphae via asexual reproduction

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Macroconidia

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large and complex conidia

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Microconidia

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small and more simple conidia

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endospores

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conidia are enclosed in a sac, the sporangium

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Presence or absence of conidia, size , shape, and location

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major features used to identify fungal species in clinical specimens

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unique morphology of Candida albicans

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ability to produce pseudohyphae: elongated cells linked together, exaggerated form of budding

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Dimorphism

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condition where fungus can exhibit yeast or hyphal form

depends on growth conditions

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Pathogenic fungi that are dimorphic

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Histoplasma
Coccidioides
Blastomyces
Sporothrix

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replication

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all fungi reproduce asexually via conidia formation
some reproduce sexually, involved genetic recombination

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Humans have high level of innate immunity to fungal infections

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resistance due to:
fatty acid content of skin
pH of skin, mucosal surfaces, and body fluids
epithelial turnover
normal flora
transferrin
mucociliary ladder in resp. tract

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Most important cellular response to fungi

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T cell immune response

individ. w/ decreased T cell response, (HIV patients) are more susceptible to fungal infections

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3 major categories of human disease due to fungi

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Mycotoxicosis
hypersensitivity diseases
colonization and diseases

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mycotoxicosis

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fungi can produce variety of toxins

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ergot alkaloids

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prod. by Claviceps purpurea
cause alpha-adrenergic blockade, causing vasoconstriction, necrosis, and gangrene
stimulate smooth muscle contraction--have been used to promote labor during birth
stimulate hypothalamus and other portions of midbrain

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Aflatoxins

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prod by Aspergillus flavus
when growing on grain
humans/cattle eat grains, potential carcinogen for humans

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Hypersensitivity diseases

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Farmer's lung
Pigeon fancier's disease

induced by fungal spores

are type III hypersensitivity rxns

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germ tubes

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prod by candida albicans to become more invasive and cause systemic disease

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visualization of fungi in tissue preparations

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treatment with 10% KOH destroys mammalian cells and allows visualization of the fungal hyphae

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Lactophenol cotton blue

positive stain

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identification of conidia arrangements and hyphae

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Grocott Silver stain or (Gomori methenamine silver)

positive stain

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identifying Pneumocystis jiroveci in sputum and bronchoscopy samples

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Dermatophyte infections

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fluorescence of fungi under UV light for visualizing

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Sabouraud's agar

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favors fungal growth bc of low pH 5.5
Nonpathogenic saprobic fungi can overgrow the pathogens

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Mycosal agar

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selective for pathogenic fungi bc chloramphenicol and cycloheximide prevents the overgrowth of saprobic fungi
Some pathogenic fungi will not grow on this media

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Hyphal morphology

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aseptate or coenocytic=Mucor, Rhizopus, Absidia

Septate: regular connection or clamp connection

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Spore morphology

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conidiospore=Penicillum, Aspergillus

sporangiospore=Rhizopus

arthrospore=Coccidioides immitis at 25 C

chlamydospore=Candida albicans in cornmeal agar

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Yeast morphology

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size and shape-broad based budding yeast=Blastomyces dermatitidis

thickness of walls

capsule presence/absence=Cryptococcus neoformans

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Fungal infection classification

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according to tissue levels initially colonized or by status of host immune system

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Superficial Mycoses

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infections limited to outermost layers of skin and hair

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Pityriasis versicolor

"Tinea versicolor"

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ID= "spaghetti and meatballs"

appearance of organism in skin scrapings

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Tinea nigra

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ID=Black, 2-celled oval yeast in skin scrapings

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Black piedra

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ID=black nodule on hair shaft:
spore sacs and spores

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White piedra

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ID=white nodule on hair shaft: mycelia that fragment in to arthrospores

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Treatment of superficial mycoses

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removing organisms from skin w/ keratolytic agents

antifungal agents can be used

shaving or cropping infected hairs

encouraging proper hygiene

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Cutaneous mycoses

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infections that extend deeper into epidermis as well as invasive hair and nail diseases

restricted to keratinized layers of skin, hair, nails

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agents causing cutaneous mycoses

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called dermatophytes

diseases are ringworm or tinea

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ID=presence/absence and shape of micro- and macroconidia in lesion scrapings

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Tinea capitis

Tinea corporis

Tinea manus

Tinea cruris="jock itch"

Tinea pedis="athlete's foot"

Tinea unguium="onychomycosis/Chronic paronychia"

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Ectothrix

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ID=mycelium and spores on hair shaft

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Endothrix

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ID=mycelium and spores in hair shaft

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cutaneous mycoses common in

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children under 12 and wrestlers

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natural reservoirs of dermatophytes

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humans-anthropophilic species
animals-zoophilic species
soil-geophilic species

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anthropophilic species

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produce mild, chronic infections

difficult to eliminate by antifungal treatment

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Sporotrichosis "Rose Handler's disease"
Handling sphagnum moss

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sporothrix schenckii
ID=budding yeast (cigar shaped) in tissue and exudate

converts to mold with "rosette pattern" of conidia on culture at 25 C

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Chromoblastomycosis

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ID=Medlar bodies in tissue

copper colored sperical yeast

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Eumycotic mycetoma
"madura foot"

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ID=white, brown, yellow, or black granules in exudate

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Systemic mycoses

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infections originate in in the lung and may spread to other organs

fungal agents are inherently virulent

focus of infection is the lung

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Histoplasmosis

common in Midwest US

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Darling's disease, cave disease, spelunker's disease

pulmonary mycosis caused by Histoplasma capsulatum

grows in high nitrogen soil

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Histoplasmosis
clinical syndromes

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infections are inapparent

only detected by residual lung calcifications and or delayed hypersensitivity to H. capsulatum

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Histoplasmosis
Lab diagnosis

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Culture and rapid DNA probe test
Saprobic phase shows tuberculate macroconidia

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Blastomycosis

common in SE and south central US

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Chicago disease, Gilchrist's disease, North american blastomycosis

agent is Blastomyces dermatitidis

characterized by granulomatous and suppurative lesions of the lung with dissemination of the skin

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Blastomycosis
clinical syndromes

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conidia become yeast in the lung
phagocytized by macrophages and carried to other parts of the body

pulmonary infection

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Blastomycosis
Lab diagnosis

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Culture: borad based-budding yeast

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Coccidioidomycosis

common in SW US desert regions

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San Joaquin valley fever, desert rheumatism, Posada-Wernicke disease

caused by Coccidioides immitis

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Coccidioidomycosis

clinical syndromes

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barrel-shaped arthroconidia (arthrospores) are inhaled

pulmonary infection

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Coccidioidomycosis

Lab diagnosis

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dimorphic with mold to spherule transition when infecting patients

spherules are multinucleate

can be stained with hematoxylin/eosin to observe spherules

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Cryptococcosis

worldwide

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Busse-Buschke disease, torulosis, European blastomycosis

inhalation of Cryptococcus neoformans

NOT dimorphic, grows as yeast in host and culture

ONLY pathogenic fungus that produces a capsue in the host and in culture

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Cryptococcosis

Clinical syndromes

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inhaled but doesn't cause respiratory problems, disseminates to meninges

most common fungal cause of meningitis is C. neoformans

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Cryptococcosis

Lab diagnosis

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India ink prep of cerebrospinal fluid sample to see the capsule

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Opportunistic mycoses

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usually affect immunocompromised people

most common
Candida albicans and Aspergillus fumigatus

Pneumocystis jiroveci (carinii) common opportunistic pathogen of pneumonia in AIDS patients

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Candidiasis

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species of Candida

underlying conditions predispose a person (pregnancy, antibiotics, AIDS, etc)

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Candidiasis
clinical syndromes

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cutaneous-intertrigo (rash in skin folds and nail folds)

mucocutaneous-perleche (cracks at corner of mouth), thrush, perianal disease

Chronic-mucocutaneous candidiasis, granulomatous disease

Systemic-UTI, endocardities, pneumonia, etc.

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Aspergillosis

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causes many diseases

A. fumigatus and A. flavus most common species

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Asperigillosis

clinical syndromes

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purely opportunistic

mycotoxicoses (ingest of contam. food)

hypersensitivity pneymonitis

secondary colonization (fungus ball)

systemic disease-invades surrounding tissues, rapidly fatal if not treated

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Zygomocosis

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spectrum of diseases similar to Aspergillus

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Zygomocosis

clinical syndromes

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Rhinocerebral zygomycosis

pulmonary zygomycosis

cutaneous zygomycosis

gastrointestinal zygomycosis

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Pneumocystis jiroveci (carinii) pneumonia

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assoc with premature and malnourished children in crowded conditions

AIDS patients and other immune deficiencies

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Pneumocystis jiroveci pneymonia
clinical syndromes

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ground-glass apprearance in lungs on chest radiograph