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- 1. MEDICAL MYCOLOGY Phan Chia Wei (PhD) Department of Pharmaceutical Life Sciences Faculty of Pharmacy phancw@um.edu.my
- 2. Armillaria solidipes Mirror mirror on the wall, who’s the largest of them all?
- 5. The international acceptance of the recognition of the macroscopic organisms of Earth as Fauna, Flora, and Funga paves the way for substantial changes in educational and agricultural policies, amongst others. This will facilitate the incorporation of mycology in matters of national interest, such as conservation, habitat protection, species protection, and education.
- 6. Pathogenic Eukaryotes • The study of fungi is called mycology • Fungi are in the Fungi kingdom. Fungi are chemo- heterotrophs and acquire food by absorption. • With the exception of yeasts, fungi are multicellular. • Most reproduce with sexual and asexual spores.
- 7. Characteristics of Fungi • Vegetative structure- fungal colonies; composed of the cells involved in catabolism and growth • Thallus – body of a mold and fleshy fungi • Long filaments of cells joined together; these filaments are called hyphae
- 8. Characteristics of Fungi • Septate hyphae → contained one nucleus • Coenocytic hyphae → no septa • Vegetative hypha → hypha that obtains nutrients • Reproductive or aerial hypha → reproduction • Hyphae grow to form a filamentous mass called a mycelium, which is visible to the unaided eye
- 9. a) Septate hyphae have cross walls, or septa, dividing the hyphae into cell-like units. (b) Coenocytic hyphae lack septa. (c) Hyphae grow by elongating at the tips.
- 10. Aerial and vegetative hyphae • A colony of Aspergillus niger grown on a glucose agar plate, showing both vegetative and aerial hyphae. • Aerial hyphae, showing reproductive spores.
- 11. Characteristics of Fungi • Yeast- non-filamentous, unicellular fungi that are typically spherical or oval. • Budding- produce up to 24 daughter cells by budding • Pseudo-hypha- buds that fail to detach themselves • Candida albicans attaches to human epithelial cells as a yeast but usually requires pseudo-hyphae to invade deeper tissues
- 12. Characteristics of Fungi • Facultative anaerobic growth • Saccharomyces species produce ethanol in brewed beverages and carbon dioxide for leavening bread dough • Dimorphism-pathogenic species-two forms of growth; as a mold or as a yeast (Histoplasma capsulatum) - histoplasmosis
- 13. Characteristic of Fungi • A micrograph of Saccharomyces cerevisiae in various stages of budding. • Candida albicans. Notice the spherical chlamydoconidia (resting bodies formed from hyphal cells) and the smaller blastoconidia (asexual spores produced by budding)
- 14. Fungal Dimorphism • Dimorphic fungi are fungi that can switch between yeast and mold, depending upon the environmental conditions. • Fungal dimorphism (Mucor indicus)
- 15. Medically Important Fungi • Zygomycota • conjugation fungi, saprophytic molds • Rhizopus stolonifer • Microsporidia • obligate intracellular parasites; lacks mitochondria • chronic diarrhea and keratoconjunctivitis most notably in AIDS patients • Encephalitozoon in pet rabbit (eye)
- 17. Medically Important Fungi • Ascomycota • sac fungi; Talaromyces; Penicillium
- 18. Medically Important Fungi • Basidiomycota • produce mushrooms
- 19. Fungal Toxins and Allergies • Mycotoxicoses (toxins) • Allergies (to fungal spores)
- 20. Fungal Toxins and Allergies • Mycotoxicosis • Amanita mushrooms • Toxins- amanitin and phalloidin (hepatoxins) • Amanitin- inhibits cellular RNA synthesis • Ergotism- caused by mold Claviceps – caused vascular and neurologic effects • Aflatoxins- coumarin derivatives produced by Aspergillus flavus - liver damage and tumors
- 21. Antifungal drugs • Antifungal drugs • Amphotericin B- binds to ergosterol and disrupts fungal cell membranes • Fluconazole- inhibits ergosterol synthesis
- 22. Fungal Diseases • Any fungal infection is called a mycosis • Five groups according to the degree of tissue involvement and mode of entry into the host: 1. Systemic 2. Subcutaneous 3. Cutaneous 4. Superficial 5. Opportunistic
- 23. Cutaneous & Subcutaneous Mycoses Superficial and cutaneous mycoses are among the most common of all communicable diseases
- 24. • Tinea pedis (foot) • Tinea unguium (nails) • Tinea manuum (hand) • Tinea cruris (groin) • Tinea corporis (body) • Tinea capitis (scalp) • Tinea faciei (face) • Tinea barbae (beard) • Tinea imbricata (overlapping pattern) • Tinea nigra (black) • Tinea versicolor (various colors) Malassezia furfur
- 25. Cutaneous & Subcutaneous Mycoses • Caused by fungi (dermatophytes) • Infect superficial keratinized structures (skin, hair, and nails) • Three genera: • Trichophyton • Epidermophyton • Microsporum
- 26. Cutaneous & Subcutaneous Mycoses • Tinea versicolor- caused by Malassezia furfur • Hypopigmented area • Fluconazole • Azoles are synthetic antifungals with broad-spectrum fungistatic activity against fungi • Azoles disrupt the synthesis of ergosterol, which is the principal sterol in fungal cell membranes
- 27. Cutaneous & Subcutaneous Mycoses • Tinea pedis (athlete’s foot) • Peeling and cracking of the skin in toe webs • Itraconazole and terbinafine • Terbinafine (allylamine antifungal) has a fungicidal effect by inhibiting the enzyme squalene monooxygenase which is involved in the synthesis of sterol in fungi. This inhibits fungal ergosterol biosynthesis by decreasing ergosterol levels.
- 28. Cutaneous & Subcutaneous Mycoses • Subcutaneous mycoses • Sporotrichosis (rose gardener’s disease) - Sporothrix schenckii • Dimorphic fungus • Mold form in plants, yeast form in human • Gardener and farmer • Itraconazole
- 29. Cutaneous & Subcutaneous Mycoses • Budding yeast cells of Sporothrix schenckii, stained black
- 30. Systemic Mycoses • Coccidioidomycosis, histoplasmosis, blastomycosis, and paracoccidioidomycosis • Coccidioidomycosis (valley fever) is caused by Coccidioides posadasii or C immitis. • Inhalation of arthroconidia leads to a primary infection that is asymptomatic in 60% of individuals • The other 40% of individuals develop fever (valley fever) • Itraconazole
- 32. Systemic Mycoses • Chest radiograph of a patient with coccidioidomycosis revealing enlarged hilar lymph nodes and a cavity in the left lung.
- 33. Systemic Mycoses • Histoplasmosis- superficially resembles tuberculosis • Histoplasma capsulatum – dimorphic • Limited geographic range in the United States • Droppings from birds and bats • Humans acquire the disease from airborne conidia • Amphotericin B or itraconazole.
- 34. Systemic Mycoses • Yeast like Histoplasma capsulatum • In soil or artificial media, it forms a filamentous mycelium carrying reproductive conidia
- 35. Opportunistic Mycoses • Yeast genus Candida are capable of causing candidiasis. • They are members of the normal flora of the skin, mucous membranes, and gastrointestinal tract • C. albicans, C. parapsilosis, C. glabrata, C. tropicalis, C. guilliermondii, and C. dubliniensis • The widespread use of fluconazole has precipitated the emergence of more azole- resistant species, such as C. krusei and C. lusitaniae. • The risk factors associated with superficial candidiasis include AIDS, pregnancy, and diabetes
- 36. Opportunistic Mycoses • Yeast invasion of the vaginal mucosa leads to vulvovaginitis. • Thrush can occur on the tongue, lips, gums, or palate. • Candidal invasion of the nails and around the nail plate causes onychomycosis. • Topical nystatin or oral ketoconazole or fluconazole; amphotericin B
- 39. Opportunistic Mycoses • Cryptococcus neoformans and C.gattii are environmental, basidiomycetous yeasts. • Yeast cells possess large polysaccharide capsules • Pigeon feces • India Ink preparation
- 40. Opportunistic Mycoses • Capsule • Cryptococcus neoformans
- 41. • The yeasts may multiply and disseminate to other parts of the body but preferentially to the central nervous system, causing cryptococcal meningoencephalitis
- 42. Opportunistic Mycoses • Aspergillosis • Aspergillus species- exist only as molds; not dimorphic • Septate hyphae that form V-shaped (dichotomous) branches • Conidia of Aspergillus form radiating chains; Mucor and Rhizopus- enclosed within sporangium • Mucormycosis- diabetic patients- mold spores in the sinuses form hyphae that invade blood vessels that supply the brain
- 43. Opportunistic Mycoses • Many people recovering from COVID-19 have of late been afflicted by black fungus – or mucormycosis – disease. • The fungus invades the sinus and makes its way into the intraorbital and intracranial regions. If its progression is not checked early, 50-80% of patients could die.