Fungi Fungal Characteristics and Human Fungal Pathogens Fungal

Fungi Fungal Characteristics and Human Fungal Pathogens

Fungal Taxonomy n Domain Eukarya n Kingdom Fungi n [True – – – Fungi = Eumycota] Phylum Zygomycota Phylum Basidiomycota Phylum Ascomycota Phylum Chytridiomycota Phylum Deuteromycota [Imperfect Fungi]

Fungal Taxonomic Names n Phylum n -mycota n Class n -mycetes n Order n -ales n Family n -aceae n Genus n Species

Fungal Characteristics n Heterotrophs n Cell wall = chitin, glucan n Mainly terrestrial n Cell membrane = ergosterol n Lack Chlorophyll n Dark Habitats n Multidirectional n Spore bearing n Nucleus n Membrane bound n Diploid chromosomes n Cytoplasm n Similar to plants n Different ribosomal synthesis n Different microtubule protein n Reproduction n Sexually (meiotic) n Asexually (mitotic) n Thallus body n Types: n Mushroom n Moulds n n Aerobic, multicelled Yeast n FA, single cell

Nutritional Status n Saphrophytes n Scavengers, recycle n Non living materials n Parasites n Feed off living materials n Mutualists n Symbionic relationship n Primarily seen with plants

Beneficial Uses of Fungi Yeasts Baking brewing Antibiotics Other Drugs penicillin cyclosporin cephalosporin Steroids Foods hormones cheeses (reproductive) Blue Roquefort Experimental metabolic pathways studied

Parasitic Fungi Overview n Cause Disease Directly n Actual fungal growth in organism n Cause Disease Indirectly n Allergic reactions n Toxin ingestion n Exhibit Dimorphism [M Y shift] n Mould form (mycelial, filamentous) n Yeast form (or spherule form) n Change due to temperature, nutrients, CO 2 levels

Mould and Yeast

Laboratory Methods to Identify n Direct Id organism in specimen fluid n Hyphae: aseptate, septate n Spore: conidiospore, arthrospore, sporangiospore n Yeast: size, thickness of walls, capsule +/Culture n Media such as Sabaurouds, BHI, Mycosal Tissue n Stains: KOH, Eosin, India ink Serology n CF, IFA Flourescence of fungi under UV light n n n

Immunity n Normal n Skin n n p. H FA Flora turnover Respiratory n cilia n Abnormal n Immunocompromised n n n n Burn HIV Chronic Disease GCC Cancers DM Post surgical Splenectomized

Fungal Infection Locations n Superficial n Cutaneous n Subcutaneous n Systemic n Lungs n Other organ systems n Opportunistic

Fungal Mould Reproduction n Sexual State n Meiotic n Teleomorph n Produce spores (conidia) n Asexual State n Mitotic n Anamorph n Produce spores (conidia)

Sexual Reproduction of Fungi

Sexual Reproduction n Sex organs called gametangia n Distinguishable male and female n Can bear sex cells (gametes) n Can bear sex nuclei (gamete nuclei) n Homothallic n Single mycelium can sexually reproduce n Heterothallic n Two mycelia are required for sexual reproduction

Reproductive Life Cycle n Growth of hyphae n Transverse fissure n Fragmentation n Break off n Spores n Sexual or asexual n Disseminate n Help in Id of fungus n Size, shape, color, number

Sexual Spores n Zygospore n Zygomycetes n Sporangium n Ascospore n Ascomycetes n Ascus rupture n Basidospore n Basidiomycetes n Gill house of basidium, pinches off

Asexual Spores n Sporangiospores n n n From sac head area called sporangium Rupture to release Zygomycetes n Conidiospores n n Free spores, not enclosed in sac Pinched off segments Ascomycetes, Basidiomycetes, Deuteromycetes Types n n n n Arthrospores Chlamydospore Blastospore Phialospore Microconidia Macroconidia Porospore

Yeast: Sacchromyces

Fungal Yeast Reproduction n Diploid Cell (via asexual reproduction) n Plentiful food n Haploid cells fuse to create diploid n Mother cell will bud diploid daughter cells n Haploid Cell (via sexual reproduction) n Starved, Undernourished environment n Meiotic division to create 4, 1 n daughters n 4 daughter spores remain inside “mother” n Released when favorable environment

Yeast on Sabauroud Agar

Phyla include most of the yeasts

Phyla include mushrooms, puff balls, shelf fungi, rusts, & smuts

Phyla include saphrophytic bread moulds and some pathogens

Phyla contain any fungus that has no known sexual repro state

Fungal Phyla for aquatic, marine

Human Mycoses Fungal Diseases of the Skin

Sporotrichosis Sporothrix schenckii n Dimorphic fungus n Reservoir: worldwide, tropical n Transmission: direct soil innoculation n DX: Special Stains n TX: Antifungals n Clinical Course n Erythematous n n Papulonodular ulcerative Lymphocutaneous n Joints n n n Ostearthritis tenosynovitis Pulmonary n CNS n Disseminated n n n Lymphatic organs GI

Sporothrix yeast phase

Sporothrix infection

CANDIDIASIS Candidia albicans n Small yeasts n Reservoir: soil, food, n n nosocomial Source: Human commensals Associated with immunocompromised DX: Id organism TX: Antifungals n Candidiasis of MM n Oropharynx n Vulvovaginal n Cutaneous n Invasive Candidiasis n Joints n GI: liver, pancreas n Urinary n Miscellaneous n Chronic n n Includes invasive areas CNS Respiratory Neonatal (thrush)

Candidia

Candidia infections: histology

DERMATOPHYTOSIS Tinea / Ringworm n Ubiquitous n Tinea capitus n Direct contact n Tinea corporis n Colonize keratin layers n Cause annular lesions with central clearing n DX: ID organism on selective media or with skin scrapings n TX: Antifungals n Tinea cruris n Tinea pedis n Tinea unguium n Tinea favosum Trichophytan Microsporum Epidermophytan

Trichophyton

Microsporum sp.

Tinea / Ringworm presentation

Trichophytan barbarae

Human Mycoses Fungal Infections of the Nervous System

CRYPTOCOCCUS Cryptococcus neoformans n Encapsulated n Worldwide n Opportunistic n Inhalation of spores n Virulence: n Enzymes n capsule n DX: Id organism n TX: Antifungals n Local in lungs n Acute = ARDS n Chronic = pneumonia n Disseminated n CNS meningitis n Cutaneous ulcers n GI inflammation liver, gall bladder, stomach n Bone ostemyelitis n Heart inflammation, all n Renal abscess n Eye inflammation, all

Cryptococcus neoformans infections

Cryptococcus in the brain

Human Mycoses Fungal Infections of the Cardiovascular System

ZYGOMYCOSIS Rhizomucor, Rhizopus, Absidia n Zygomycetes group n n Soil, decay n Opportunistic n n Invades arteries causing embolus n DX: Autopsy, Culture, Histopath n TX: Antifungals n PX: usually fatal n n n Rhinocerebral n DM n Orbital structures n Internal Carotid Pulmonary n Neutropenic n dyspnea n hemoptysis GI n Malnutrition n Intraabdominal abscess Cutaneous n Skin trauma, burns n Necrotic lesions Other areas Bone n Heart n

Rhizomucor, Rhizopus Rhizomucor Rhizopus

Human Mycoses Fungal Infections of the Respiratory System

ASPERGILLOSIS Aspergillus sp. n Allergic n Soil, decay n Inhalation of spores n Opportunistic n Pulmonary Dz n Immunocompromised n DX: Id organism in fluids, culture, histopathology n TX: Antifungals n Px: Mortality rate is 50100% Bronchopulmonary n Sinuses and lungs n n Pulmonary n Within paranchyma n Invasive n CNS n Bone osetomyelitis n Heart endocarditis n Renal abscess n Cutaneous n n Ear post op, sx Catheter placement Burn victims

Aspergillosis Infections Culture specimen

Aspergillus histology

Coccidioidomycosis Coccidioides immitis n Dimorphic fungi n n Western hemisphere in n n n arid regions Inhalation of spores Spores transform to spherules DX: CF, RADS, Isolation, Direct ID TX: Antifungals PX: 90% resolve spontaneously unless immunocompromised n Asymptomatic Acute n Respiratory: SOB, pain n Skin: rash Chronic n Pulmonary Nodules Disseminated n Skin: ulcerative n Joints: synovitis n Meninges: hydrocephalus n Any other organs n Internal linings n GI n Urogenital n Endocrine

Coccidioidomyces

Coccidioides immitis: Spherules

Coccidiodes clinical presentation

Paracoccidioidomycoses Paracoccidioides brasiliensis n South America n n Soil, decayed wood n Inhalation of blastoconidia n DX: Id organism in specimens, culture, histopathology n TX: Antifungals n PX: good if treated, possibility of relapse n n Asymptomatic n Dormant n Reappear if immunocompromised MM n Ulcerations of mouth and oropharynx Pulmonary n Nodular infiltrates n Mimic TB Cutaneous n Ulcerative n Invasive to S. C. Disseminated GI: liver n Bones n CNS n Male genitourinary tract n

Paracoccidioides KOH Microscopic Yeast Phase Macroscopic

BLASTOMYCOSES Blastomyces dermatitidis n Dimorphic, heterothallic ascomycete n SC, SE US : Mississippi and Ohio River Valleys n Source Soil, rotting wood n Growth in feces of bats, birds n n n Inhalation of conidia n DX: Direct Id of fluid specimens, Culture, Histopathology n TX: Antifungals n PX: spontaneous resoluton, Tx CNS infections n Asymptomatic n 50% of infections Acute Pulmonary n Mimics bacterial infections Chronic Pulmonary n Mimics bronchogenic carcinoma Disseminated n Skin: ulcerative n Bones: long bones, lytic n Genitourinary n n Male: ducts, glands Others n CNS n Pericardium n GI n Adrenal Gland

Blastomyces: Yeast Phase

HISTOPLASMOSIS Histoplasma capsulatum n Dimorphic fungus n Soil n n n Inhalation of microconidia n DX: Direct Id of fungi in specimen sample, histopathology, culture n TX: Antifungals n PX: most are self limited, Tx if respiratory and disseminated Subclinical, benign Acute n n Chronic Pulmonary ~ TB Fibrosing Mediastinitis n n n Self limited, flu-like symptoms Pulmonary: pneumonitis, calcification Pericarditis Rheumatological: arthritis Fibrous CT in mediastinum Affects surrounding structures Disseminated n n n n Lymphadenitis Red bone marrow suppression Endocarditis CNS: meningitis, cerebritis GI: ulcers Skin: rash Genitourinary of males Eyes: uveitis, chorioditis

Histoplasmosis

Histoplasmosis: Disseminated

Histoplasmosis Culture Id Clinical Presentation Cytology

Human Mycoses Environmental Moulds

Environmental Exposure n Allergic n Prior Exposure n Re-exposure n Respiratory signs n n n Coughing Wheezing Sinus congestion Rhinorrhea Itchy nose Sore throat n Mycotoxins n Ingestion n Ergotism – – n Claviceps Rye products Limb gangrene Alpha adrenergic blockade Aflatoxins – Aspergillus – Peanut meal – carcinogens n Zearalenones – Fusarium – Estrogen like steroid – Precocious puberty

Psychotropic agents n Psilocybin n Psilocin n Lysergic Acid Diethylamide

Not all toxins are bad…. . n Penicillium sp. n Griseofulvin n Antimycotic action Systemic use Disrupts mitotic spindle by binding to microtubule protein

Antifungals n n n Macrolides: n Bind to ergosterol to disrupt osmotic integrity of plasma membrane n Amphotericin B, Nystatin Azoles n Block ergosterol and chitin synthesis by inhibiting cytochrome P-450 enzymes, causes accumulation of product that replaces ergosterol n Topical and /or systemic: Oral, IV, intrathecal, suppository n Ketaconazole, Itraconazole, Fluconazole, Clotrimazole, Miconazole Allylamines: n Binds to enzyme involved with ergosterol synthesis, thereby blocking n Terbinafine (Lamisil) Pyrimidine Analogs n RNA incorporation in place of uracil n DNA synthesis blockage by enzyme binding n Flucytosine fluracil (RNA) further metabolites for DNA action Miscellaneous n Griseofulvin: disrupts mitotic spindle n Others with unkown MOA that have antifungal functions n Haloprogin, Ciclopirox, Tolnaftate, KI

Fungal Disease Summary n Zygomycota n Rhizopus, Rhizomucor n Ascomycota n Aspergillus, Blastomyces, Histoplasmosis, Dermatophytes: Trichophyton, Microsporum, Epidermophyton n Deuteromycota n Sporothrix, (Para)Coccidioides, Candidia n Basidiomycota n Cryptococcus

Questions? n Would you give an antibiotic to a person with a fungal infection? n How would you prevent self exposure when working with a patient with a fungal disease?