Mycology

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Fungal Toxins & Allergies

, there are two other kinds of fungal disease: Mycotoxicoses, caused by ingested toxins. Allergies to fungal spores. The best-known mycotoxicosis occurs after eating Amanita mushrooms. These fungi produce five toxins, two of which are among the most potent hepatotoxins. Amanitin and Phalloidin

Fungi grow as

-heterotrophs that are saprophytes decomposing dead and dying material,using it as food -excrete extracellular enzymes that digest their food outside their cells -live in air, water, soil, plants and animals -grow on sabouraud's dextrose agar at 25 (mold) or 37 degrees C (yeast). growth aided by antibacterials

Hyalohyphomycosis

Acremonium, Fusarium, Penicillium, Scopulariopsis: mono mold worldwide, ingestion, inhalation, or contact, no imm thrombosis and infarction of tissue pumonary, cerebral, cutaneous, gastrointestinal, and ocular granulomas diag: large hyaline hyphae amp B

Otomycosis

Aspergillus, Penicillium, Mucor, Rhizopus, monomorphic mold, infection of ear worldwide, spread by contact, no immunity results in accumulation of eipth. debris in ext. aud. meatus Diag: fragments of mycelium w/ septa Ketoconazole or wax hook

Aspergillosis

Aspergillus: mono yeast worldwide, implantation, inhalation, contact, no imm presence of dsRNA mycoviruses represses the formation of toxins. endothelial necrosis pulmonary: asthma. bronchitis disseminated: proptosis, growth of heart valves, lesions on organs diag: acute angle branches amp B

Candidiasis

Candida albicans: mono yeast worldwide, by contact or nosocomially, no immunity emboli of brain, spleen, and kidneys Trush: glossitis, stomatitis, cheilitis, perleche, vag, bal cutan: paryonychia, diaper rash systemic: heart murmur, hepatosplenomegaly, etc diag: pseudohyphae w/ constrictions at septa fluconazole or amp B

Coccidiodomycosis

Coccidioides immitis: DIMORPHIC ARID REGIONS OF SW US AND CENTRAL AND S AMERICA inhalation of arthrospores, PROTECTIVE IMMUNITY pulmonary: asymp, or fever chills, cough, anorexia valley fever allergic: desert bumps arthritis: desert rheumatism disseminated: meningitis, verrucous granulomas, or miliary lesions diag: thin walled sperules with endospores amp B

phylum Zygomycota pathogenic

Conjugation fungi. sexual reproduction takes place by simple copulation of the tips of multinucleated hyphae forming large thick walled zygospores that are resistant to harsh environmental conditions

Cryptococcosis

Cryptococcus neoformans, gattii: mono yeast worlwide in pigeon dung, eucalyptus trees, partial imm capsular polysaccharide inhibits immunity Meningoencephalitis pulmonary: cough, fever, headache, etc cutaneous: papules, ulcers mucocutaneous: swollen nodes, granulomas Disseminated: meningitis and lesions in heart osseous: swelling and pain in bones diag: thick polysaccharide capsule forms halo Fluconazole

Tinea nigra Causal agent: Cladosporium werneckii. Also called Hortaea werneckii Exphiala werneckii

HORTAE WERNECKII:black mold superficial mycosis of palm and feet, monomorphic mold worldwide, no immunity spread by contact mold feeds on stratum corneum, growing black lesions diagnose:multibranched septa dark hyphae, melanized cell walls looks like melanoma Miconazole

Histoplasmosis

Histoplasma: DIMORPHIC worlwide, heavy concentration in ohio-miss valley, also africa and asia, inhalation of spores, PROTECTIVE IMM necrotic granulomas and lesions containing infected monocytes and macrophages that grow in bone marrow pulmonary: summer fever mucocutaneous: oropharyngeal ulcer systemic: fever, anemia, meningitis, etc, septic shock diag: extra of intracellular oval yeasts with bud scars and thin walls amp B

Diagnostic tests

KOH(dissolves human tissue, leaving only fungal), Per-iodic acid schiff(stains polysaccharides found in cell wall of fungi), giemsa stain(for intracellular structure, stains intracellular yeast blue), nigrosin stain(demonstrates capsules around cells). Circulating IgG and IgM are produced in response to fungal infection, Calcofluor white is a fluorescent dye that binds to fungal cell walls and is useful in the identification of fungi in tissue specimens. Methenamine silver stain is also useful in the microscopic diagnosis of fungi in tissue. Fungi are frequently cultured on Sabouraud's agar It facilitates the appearance of the slow-growing fungi by inhibiting the growth of bacteria in the specimen. complement fixation test Capsular antigens

Lobomycosis

Lacazia loboi: mono yeast, subcutaneous S. and Central america and florida, humans and dolphins by traumatic contact, no immunity mold spores release toxic compounds->inflamm. resp.->granulomas painless plaques->tumor like areas of infection diag: lemon shaped yeast joined by short tubes Surgical Excision

Tinea Capitis-Ectothrix

MICROSPORUM: mono mold, cutaneous mycosis of scalp worldwide, by contact or air, partial immunity Conidia outside hair shaft gray-patch ringworm. allergic reactions produce dermatophytids, itching, keratomycosis diag: chains of macroconidia Griseofulvin

Pityriasis (tinea) versicolor. Malassezia globosa M restricta M furfur complex Asymptomatic, cosmetic

Malassezia FURFUR - lipophilic, not truly DIMORPHIC fungus causes superficial mycotic infection of skin Found worldwide, no immunity spread by contact, people that use lipid emulsions, have illness, malnutrition, high cortisol levels and high temp and humidity are more at risk infection occurs when fungus feeds on skin oil and removes stratum corneum layer resulting in squamous cell turnover of the outer epithelium. lesions are red, brownish, blotchy, scaly, hyper/hypo pigmented. can develop into itchy papules and pustules or atopic dermatitis, dandruff, discolored skin, folliculitis Diagnose: stubby hyphae, and globose budding yeast cells in form of spaghetti and meatballs, microscopic examination of scrapings of infected skin, treated with 10-20% KOH or stained with calcofluor white. Treatment: Ketoconazole, Daily applications of selenium sulfide.

Mucormycosis

Mucor, Absidia, Rhizopus: mono mold worldwide, implantation, ingestion, inhaltion in sick pts no immunity hyphae invade bloodvessels, cause necrossi, thrombosis, and infarction. true medical emergencies in immunosuppressed, diabetic, or neutropenic thoracic: fever, dyspnea, bronchitic, peneumonia Rhinocerebral: fever, headache, proptosis swelling of brain abdominal: gastrointestinal ulcers, diarrhea, peritonitis cutaneous: dues to bandages, get granulomas CNS: occurs in debilitated pts due to invasion of nose or paranasal sinuses or head trauma diag: broad, branching, non-septate, right angle hyphae amp B

phylum Basidiomycota pathgenicc

Mushrooms. Club Fungi. sexual reproduction produces basidiospores that are formed on a club shaped structure called a basidium

Black piedra

Piedra hortae - black mold that produces superficial mycosis of hair shafts, monomorphic mold Found in S. America, no immunity Transmission: person-person, mammal-person, contact with contaminated fomites weakening of hair due to keratinolytic activity. Hard black encrustations of hyphal cells form nodule on hair shaft. black dandruff cross section of hair show black, gritty nodules containing multi-ascopore asci selenium sulfide (selsen blue)

Rhinosporidiosis

Rhinosporidium seeberi: mono mold, subcutaneous world wide, inhalation or contact, no immunity polyp develops in mucosa (nasal form) ocular: sessile/stalked growth in conjunctiva Cutaneous: wart like lesion systemic: polyp growth in organs diag: thick walled sporangia w/ endospores amphotericin b

phylum Ascomycota largest onw

Sac fungi. sexual reproduction results in an ascus, a saclike structure containing four to eight ascospores

Sporotichosis

Sprothrix schenckii: DIMORPHIC, subcutaneous worldwide, traumatic implantation or inhalation,no imm lesions in lymphatics (lymphocutaneous) ulcers on skin (fixed cutaneous) ulcer in mucosa (mucocutaneous) lung lesions (pulmonary) lesion in eyes, bone, other organ (extracutaneous) diag: cigar shaped yeast, asteroid bodies Itraconazole

White Piedra

TRICHOSPORON OVOIDES:monomorphic mold, mycosis of hair shaft worldwide, no immunity spread by contact white nodular swelling on shaft of hair (dandruff) diagnosis:conidia w/ white nodules Selenium sulfide Black piedra A nodular infection of the hair shaft caused by Piedraia hortai.

Antifungal therapy

The selective toxicity of amphotericin B and the azole group of drugs is based on the presence of ergosterol in fungal cell membranes Amphotericin B binds to fungal cell membranes at the site of ergosterol and disrupts the integrity of the membranes. Azole drugs, such as itraconazole, fluconazole, and ketoconazole, inhibit the synthesis of ergosterol. echinocandins, such as caspofungin, is based on the presence of a cell wall in fungi, whereas human cells do not have a cell wall. Echinocandins inhibit the synthesis of D-glucan, which is a component of the fungal cell wall.

Tinea Faciei

Trychophyton, monomorphic, cutaneous mycosis on parts of face with no skin worldwide, by contact or air, partial immunity circular lesions w/ raised margins diag: hyphae w/ microconidia Miconazole

Tinea Capitis-Endothrix

Trychophyton: mono mold, cutaneous mycosis of scalp worldwide, by contact or air, partial immunity Black dot ringworm: circular lesions w/ black dots diag: Conidia inside hair shaft Griseofulvin

Tinea Barbae

Trychophyton: monomorphic mold, cutaneous mycosis of face where there is hair found worldwide, contact or air, partial immunity mycelia grow into pores around hair produce edema and destruction of skin proteins leads to scaling lesions, or pustules on bearded areas diag: different types of microconidia Griseofulvin

Coenocytic hyphae are

analogous to septa but complete opposite. they are hyphae w/ nuclei in a continuous mass of cytoplasm

Other ingested toxins, aflatoxins

are coumarin derivatives produced by Aspergillus flavus, which cause liver damage and tumors in animals and are suspected of causing hepatic carcinoma in humans. are ingested with spoiled grains and peanuts and are metabolized by the liver to the epoxide, a potent carcinogen. Aflatoxin B1 induces a mutation in the p53 tumor suppressor gene, leading to a loss of p53 protein and a consequent loss of growth control in the hepatocyte

Fungi secrete enzymes that ....

are virulence factors b/c they cause host cell damage and impair antifungal host defenses -toxins act as allergins and cause granuloma -mannan (found in fungal cell wall) suppresses lymphoblast formation and keratinocyte proliferation

anamorphs

asexual spores, that can be simple, single-celled bodies or multicellular

Fungi reproduce asexually by

budding (unequal division of a cell), fragmentation (pieces of hyphae grow) or by spore formation (haploid cells) followed by dispersal

Homo vs Heterothallic reproduction

cells of single colony vs cells of different colonies engage in sexual reproduction

Septa are

cross walls that divide hyphae into individual cells. septa have pores which organelles can move from cell to cell

Amphotericin B and nystatin

depletes ergosterol in cytoplasmic membranes increasing membrane permeability

Fungal cells have

eukaryotic nuclei, mitochondria, ER, bilayered cell membrane, SOFT CELL WALL, some have a polysaccharide capsule that prevents drying and protects against macrophages . Fungi cell wall are made of the polysaccharides: mannan, glucan, and chitin In fungi, the dominant sterol is ergosterol In mammalian cells, it is cholesterol. Fungal cell structures are important medically. The cell wall are insensitive to antibiotics, such as penicillin because they contain chitin β-glucan in fungal cell wall is the site of action of the antifungal drug caspofungin. Some yeasts and molds have melanized cell walls, imparting a brown or black pigment; such fungi are dematiaceous

Examples of Vegetative molds

favic chandelier-structures that are multiple branched hyphal ends knotted hyphae-form nodular structures. sticky, facilitate transport pectinate bodies-hyphal projections, look like broken combs racquet mycelia-hyphae that consist of a chain of segments, each with an enlarged end spirals/coiled hyphae-bedspring like helical coils

macroconidia

form at the tips of hyphae and are large and contain more than one spore

microconidia

formed at the tips of hyphae and are small and unicellular

Molds

have hyphae that grow by longitudinal extension and produce spores. can form mycelia (clumps of intertwined hyphae

Arthrospores

hyphal segments that are formed by fragmentation of hyphae Eg. Coccidioides immitis

Pentamidine isethionate

inhibits DNA, RNA, phospholipids and protein syn, resulting in disruption of nuclear metabolism

Fluconazole, itraconazole, ketoconazole, -zole

inhibits ergosterol syn. by preventing conversion of lanosterol to ergosterol, resulting in loss of cell membrane integrity

Griseofulvin

inhibits fungal mitosis at metaphase by disrupting mitotic spindles

Flucytosine

interferes with pyrimidine metabolism, inhibits RNA and DNA syn.

Another mycotoxicosis, ergotism

is caused by the mold Claviceps purpura, which infects grains and produces alkaloids (e.g., ergotamine and lysergic acid diethylamide [LSD]) that cause pronounced vascular and neurologic effects.

pseudophyphae

long chains of elongated yeast cells

Pathogenic symbionts are either...

necrotrophic (facultative pathogens that live on damaged tissue and bring about the death of their host) or biotrophic parasites (obligate pathogens, dependent on living host tissue)

Fungal culture growth rate

normal growth = virulent lower growth rate = avirulent -different virulence genes are expressed during different types of infections -fungi that lack invasive enzymes are avirulent

phylum Deuteromycota Chytridiomycota

reproduce asexually, producing conidia. this is the phyla that contains many infectious fungi

telomorphs

sexual reproductive structures

Fungi can grow as

single cells called yeast, or as multicellular colonies call molds (as long filaments (hyphae) and form a mat (mycelium). Some Hyphae are divided by transverse or cross walls Septate hyphae, (present) Non-septate hyphae(absent) Nonseptate hyphae are multinucleated Coenocytic Hyphae that penetrate the supporting medium and absorb nutrients are The vegetative or substrate hyphae. In contrast, hyphae that project above the surface of the mycelium and usually bear the reproductive structures of the mold are Aerial hyphae

sporangia

spherical, sac like structures containing sporangiospores. these break out and fly through air. eg Rhizopus and Mucor. Blastospores -another. Ex of sexual spore Are formed by the budding process by which yeasts reproduce asexually (some yeasts, e.g., Can. albicans, can form multiple buds that do not detach, thus producing sausagelike chains called pseudohyphae, which can be used for identification).

holomorphs

the whole fungus

Are fungi monomorphic or dimorphic

they can be both. can grow as yeast at body temp and as mold at room temp

Fungi are chemoheterotrophic meaning.....

they obtain carbon from non-living organic material as saprophytes or from living tissues as symbionts

chlamydospores

thick walled spores that are formed terminally or w/in hyphal segments eg the terminal chlamydospores of Can. albicans aid in its identification).

Allergies

to fungal spores, particularly those of Aspergillus, are manifested primarily by An asthmatic reaction (rapid bronchoconstriction mediated by IgE), Eosinophilia A "wheal and flare" skin test reaction.

Terbinafine

toxicity due to toxic accumulation of squalene that depletes ergosterol in cell membrane

Examples of sexual spores. Fungi that do not form sexual spores are termed "imperfect" and are classified as Fungi imperfecti or Dueteromycetes Most fungi of medical interest propagate asexually by forming conidia (asexual spores) from the sides or ends of specialized structures.

zygospores, ascospores, and basidiospores. Zygospores are single large spores with thick walls Ascospores are formed in a sac called ascus Basidiospores are formed externally on the tip of a pedestal called a basidium.


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