FUNGI David Dockrell Professor of Infectious Diseases University of Sheffield

Pathogens and commensals Organism that causes or is capable of causing disease Commensal Organism which colonises the host but causes no disease in normal circumstances Opportunist Pathogen Microbe that only causes disease if host defences are compromised Virulence/Pathogenicity The degree to which a given organism is pathogenic Asymptomatic carriage When a pathogen is carried harmlessly at a tissue site where it causes no disease

Nomenclature Candida albicans

Nomenclature Candida (genus) albicans (species)

FUNGI Saprophytes, Parasites or Commensals Eukaryotic Soils, Foods, Animal Droppings Well-defined cells walls composed of polysaccharides and chitin Can be MOULDS or YEASTS or dimorphic

FUNGI Cells of fungi pathogenic to humans are non-motile. Fungal cell walls have a rigid cell wall composed of polysaccharides and chitin. The fungal cell wall stains with Gomorra methenamine silver and while still viable the periodic acid-Schiff reagent. Most fungi stain too weakly with the Gram-stain but Candida may appear gram-positive. Most fungi lack a capsule with the exception of Cryptococcus which has a characteristic polysaccharide capsule. Inside the cell wall is the sterol-rich cytoplasmic membrane the target of azole and polyene antibiotics.

Yeasts and Moulds Yeasts Unicellular Reproduce by budding (asexual)

FUNGI Yeasts are round or oval. Reproduce by budding. Some yeasts such as Candida albicans can grow in tissue either as typical round or oval forms but bud as tubular forms termed pseudohyphae. Dimorphic fungi grow as yeasts in tissue but as moulds in-vitro at room temperature.

FUNGI Moulds are composed of tubular structures called hyphae. Moulds grow by longitudinal extension and branching to form an interwoven mycelium. Reproduce by spore formation. Aspergillus spp. have septate hyphae, agents of mucormycosis lack septa.

Yeasts and Moulds Yeasts Moulds Unicellular Reproduce by budding (asexual) Moulds Composed of branching filaments called hyphae Grow by apical extension into an interwoven mycelium Reproduce by spore formation –sexual/asexual

Classification of Fungi 1. Yeasts Canida albicans and non-albicans candida Cryptococcus neoformans Malassezia furfur Histoplasma, Blastomyces, Coccidioides, Paracoccidioides Penicillium marneffei 2. Dimorphic fungi Sporothrix schenckii 3. Moulds (Filamentous fungi) Aspergillus spp., Fusarium spp. Mucoraceous moulds Trichophyton spp. Dark -walled fungi

Types of fungal infection Superficial mycoses Subcutaneous mycoses Systemic mycoses

Superficial mycoses Common infections of skin, hair, nails, mucous membranes RINGWORM Dermatophytes – moulds Colonise keratin Animals and humans Tinea infections Nail infections (onychomycosis) can be caused by other fungi as well YEAST INFECTIONS Skin, nails and mucous membranes Generally endogenous, but can be sexually transmitted Candida spp, (thrush) Malassezia furfur (Pityriasis versicolor)

Chronic cutaneous or subcutaneous fungal infections Chromomycosis. World-wide , but most common in tropics. Caused by pigmented fungi with septate dark brown cells singly or in clusters. (sclerotic bodies). -Verrucous or annular lesions. Mycetoma (Madura foot). Chronic and locally destructive. fungal or Non-fungal. Tropical. Papule develops swelling. triad; sinus, swelling and grain filled pus.

SYSTEMIC MYCOSES – PRIMARY PATHOGENS Histoplasma capsulatum (histoplasmosis) Inhalation of spores from moulds Dimorphic fungi Americas Coccidioides immitis (coccidiodomycosis) Blastomyces dermatidis Penicillium marneffei

SYSTEMIC MYCOSES –OPPORTUNIST PATHOGENS Aspergillus fumigatus Aspergillus niger Candida albicans Cryptococcus neoformans Immunosuppressed patients (Cancer, AIDS) Multiorgan disease moulds yeasts

Diagnosis of fungal infection Selection of Specimens Skin, hair, nail clippings, swabs, biopsies Staining of body fluids with KOH (Fungi also detected on Giemsa or gram stain). Staining tissue samples with Gomori methenamine silver stain or periodic acid-Schiff reagents. Specific Indian Ink stain for Cryptococcus neoformans. Histopathologic review of biopsy specimens.

Diagnosis of fungal infection Culture Sabourauds agar (contains antibiotics) Culture (For filamentous fungi and dimorphic fungi hazardous, often only by reference mycology units). Serology; Dimorphic fungi. Antigen detection for Cryptococcus and Histoplasma. Aspergillus (Galactomannan). PCR based diagnosis for Aspergillus.

CANDIDIASIS Mucous membranes of mouth and vagina Candida spp. (C.albicans, C.glabrata, etc) Commensal yeasts Cause disease when normal microflora disturbed Steroids antibiotics Immunosuppression (eg AIDS) Treatment with topical nystatin, ketoconazole, oral fluconazole

RINGWORM INFECTION (DERMATOPHYTOSIS, TINEA) Tricophyton spp. eg T.rubrum Microsporum spp. Epidermophyton spp. Direct or indirect transfer of infected keratin (eg communal bathing facilities) Ringworm, athletes foot (Tinea pedis), swimmers crotch (Tinea cruris) Diagnosis by skin scrapings, Woods lamp

PITYRIASIS VERSICOLOR Malassezia furfur Discolouration of skin Young adults Topical therapy

ASPERGILLOSIS Aspergillus spores ubiquitous in soils and dusts Mainly affects lungs Invasive aspergillosis Neutropaenic patients Treatment with amphotericin Allergic aspergillosis In some chronic asthmatics (ABPA) Aspergilloma Fungus ball in pre-existing cavity of lung

CRYPTOCOCCOSIS Cryptococcus neoformans Capsulate yeast Associated with pigeon droppings Disease of immunosuppression (eg AIDS) Inhalation Lung Disease, meningitis Diagnosis by India ink staining, or detection of capsular antigen (CSF or blood) Treatment with amphotericin B or azoles

TREATMENT OF FUNGAL INFECTIONS They are eukaryotes Drugs target sterols in cell membranes Topical (eg nystatin, ketoconazoe) Systemic Oral (eg fluconazole and other azoles) Parenteral (eg amphotericin)

Antifungal therapy Inhibit ergosterol biosynthesis Binding to sterols in cell wall and destabilizing it Inhibit ergosterol biosynthesis Inhibit DNA and RNA synthesis Inhibit microtubule assembly

Antifungal therapy Class Compounds Mechanism Uses POLYENE Amphotericin B Nystatin Bind to sterols and destablise cell membrane Systemic disease topical disease AZOLE Clotrimazole, Miconazole ketoconazole, Fluconazole, Itraconazole, Voriconazole, Posaconazole Inhibit ergosterol biosynthesis Topical disease Systemic disease ALLYLAMINE Terbinafine Superficial infections including onychomycosis ECHINOCANDIN Caspofungin Anidulafungin,Micafungin Inhibit the formation of cell wall glucan PYRIMIDINE 5-fluorocytosine Inhibit DNA and RNA synthesis GRISAN Griseofulvin Inhibit microtubule assembly