Fungi

Fungal Characteristics and Human Fungal Pathogens Fungal Taxonomy

„ Domain Eukarya „ Kingdom Fungi „ [True Fungi = Eumycota] – Phylum Zygomycota – Phylum Basidiomycota – Phylum Ascomycota – Phylum Chytridiomycota – Phylum Deuteromycota [Imperfect Fungi] Fungal Taxonomic Names

„ Phylum „ -mycota „ Class „ -mycetes „ Order „ -ales „ Family „ -aceae „ Genus „ Species Fungal Characteristics

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

„ Saphrophytes „ Scavengers, recycle „ Non living materials „ Parasites „ Feed off living materials „ Mutualists „ Symbionic relationship „ Primarily seen with plants Beneficial Uses of Fungi

Yeasts Antibiotics Other Drugs Baking penicillin cyclosporin brewing cephalosporin

Steroids Foods Experimental hormones cheeses metabolic (reproductive) Blue pathways Roquefort studied Parasitic Fungi Overview

„ Cause Disease Directly „ Actual fungal growth in organism „ Cause Disease Indirectly „ Allergic reactions „ Toxin ingestion „ Exhibit Dimorphism [MÆY shift] „ Mould form (mycelial, filamentous) „ Yeast form (or spherule form) „ Change due to temperature, nutrients, CO2 levels Mould and Yeast Laboratory Methods to Identify

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

„ Normal „ Abnormal „ Skin „ Immunocompromised „ Burn „ pH „ HIV „ FA „ Chronic Disease „ Flora „ GCC „ turnover „ Cancers „ Respiratory „ DM „ cilia „ Post surgical „ Splenectomized Fungal Infection Locations

„ Superficial „ Cutaneous „ Subcutaneous „ Systemic „ Lungs „ Other organ systems „ Opportunistic Fungal Mould Reproduction

„ Sexual State „ Meiotic „ Teleomorph „ Produce spores (conidia) „ Asexual State „ Mitotic „ Anamorph „ Produce spores (conidia) Sexual Reproduction of Fungi Sexual Reproduction

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

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

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

„ Sporangiospores „ From sac head area called sporangium „ Rupture to release „ Zygomycetes „ Conidiospores „ Free spores, not enclosed in sac „ Pinched off segments „ Ascomycetes, Basidiomycetes, Deuteromycetes „ Types „ Arthrospores „ Chlamydospore „ Blastospore „ Phialospore „ Microconidia „ Macroconidia „ Porospore Yeast: Sacchromyces Fungal Yeast Reproduction

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

„ Clinical Course „ Dimorphic fungus „ Erythematous „ Reservoir: „ Papulonodular worldwide, tropical „ ulcerative „ Lymphocutaneous „ Transmission: direct „ Joints soil innoculation „ Ostearthritis „ tenosynovitis „ DX: Special Stains „ Pulmonary „ TX: Antifungals „ CNS „ Disseminated „ Lymphatic organs „ GI Sporothrix yeast phase Sporothrix infection CANDIDIASIS Candidia albicans „ Candidiasis of MM „ Small yeasts „ Oropharynx „ Reservoir: soil, food, „ Vulvovaginal nosocomial „ Cutaneous „ Source: Human „ Invasive Candidiasis commensals „ Joints „ GI: liver, pancreas „ Associated with „ Urinary immunocompromised „ Miscellaneous „ DX: Id organism „ Chronic „ TX: Antifungals „ Includes invasive areas „ CNS „ Respiratory „ Neonatal (thrush) Candidia Candidia infections: histology DERMATOPHYTOSIS Tinea / Ringworm „ Ubiquitous „ Tinea capitus „ Direct contact „ Tinea corporis „ Colonize keratin layers „ Tinea cruris „ Cause annular lesions with central clearing „ Tinea pedis „ DX: ID organism on „ Tinea unguium selective media or with „ Tinea favosum skin scrapings „ TX: Antifungals Trichophytan Microsporum Epidermophytan Trichophyton Microsporum sp. Tinea / Ringworm presentation Trichophytan barbarae Human Mycoses

Fungal Infections of the Nervous System CRYPTOCOCCUS Cryptococcus neoformans „ Encapsulated „ Local in lungs „ Acute = ARDS „ Worldwide „ Chronic = pneumonia „ Opportunistic „ Disseminated „ Inhalation of spores „ CNS Æ meningitis „ Cutaneous Æ ulcers „ Virulence: „ GI Æ inflammation liver, „ Enzymes gall bladder, stomach „ capsule „ Bone Æ ostemyelitis „ DX: Id organism „ Heart Æinflammation,all „ Renal Æ abscess „ TX: Antifungals „ Eye Æ inflammation, all Cryptococcus neoformans infections Cryptococcus in the brain Human Mycoses

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

Rhizomucor

Rhizopus Human Mycoses

Fungal Infections of the Respiratory System ASPERGILLOSIS

Aspergillus sp. „ Allergic „ Bronchopulmonary „ Soil, decay „ Sinuses and lungs „ Inhalation of spores „ Pulmonary „ Opportunistic „ Within paranchyma „ Pulmonary Dz „ Invasive „ Immunocompromised „ CNS „ DX: Id organism in „ BoneÆ osetomyelitis fluids, culture, „ HeartÆendocarditis histopathology „ RenalÆ abscess „ TX: Antifungals „ Cutaneous „ Px: Mortality rate is 50- „ post op, sx 100% „ Catheter placement „ Burn victims „ Ear Aspergillosis

Infections Culture specimen Aspergillus histology Coccidioidomycosis Coccidioides immitis

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

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

KOH

Microscopic Yeast Phase

Macroscopic BLASTOMYCOSES Blastomyces dermatitidis

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

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

Culture Id

Clinical Presentation Cytology Human Mycoses

Environmental Moulds Environmental Exposure

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

„ Psilocybin „ Psilocin „ Lysergic Acid Diethylamide Not all toxins are bad…..

„ Penicillium sp. „ Griseofulvin „ Antimycotic action „ Systemic use „ Disrupts mitotic spindle by binding to microtubule protein Antifungals

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

„ Zygomycota „ Rhizopus, Rhizomucor „ Ascomycota „ Aspergillus, Blastomyces, Histoplasmosis, Dermatophytes: Trichophyton, Microsporum, Epidermophyton „ Deuteromycota „ Sporothrix, (Para)Coccidioides, Candidia „ Basidiomycota „ Cryptococcus Questions?

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