1. FUNGI David Dockrell Professor of Infectious Diseases
University of Sheffield

2. 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

3. Nomenclature
Candida albicans

4. Nomenclature
Candida (genus) albicans (species)

5. 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

6. 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.

7. Yeasts and Moulds
Yeasts
Unicellular
Reproduce by budding (asexual)

8. 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.

9. 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.

10. 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

11. 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

12. Types of fungal infection
Superficial mycoses
Subcutaneous mycoses
Systemic mycoses

13. 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)

14. 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.

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

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

17. 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.

18. 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.

19. 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

20. 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

21. PITYRIASIS VERSICOLOR
Malassezia furfur
Discolouration of skin
Young adults
Topical therapy

22. 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

23. 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

24. 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)

25. 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

26. 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