PM-250 Fungi 1 Lecture 2024 PDF

PM-250 Fungi 1 Medically Important Fungi Dr Claire Price [email protected] Fungi Kingdom Mycology – study of Fungi Large kingdom Most fungi saprophytic Multicellular – mushrooms, truffles, moulds Unicellular – yeasts Important source of toxins, antimicrobials, food and used in food product...

PM-250 Fungi 1 Medically Important Fungi Dr Claire Price [email protected] Fungi Kingdom Mycology – study of Fungi Large kingdom Most fungi saprophytic Multicellular – mushrooms, truffles, moulds Unicellular – yeasts Important source of toxins, antimicrobials, food and used in food production Fungi In the air, soil etc. Also part of microbiota Mainly non-pathogenic. Can be commensal (endogenous), or environmental (exogenous) Emergence of AIDS and immunosuppressive treatments has highlighted the importance of fungal disease >300 million serious infections per year Kill more people than malaria Outline Morphology, cell structure features General life cycle Classification of medically important fungi General pathogenesis, immunity and virulence ◦ Lecture 2 = Mycoses, immune response ◦ Lecture 3 = Antifungal treatment and resistance Medically Important Fungi Eukaryotes Rigid cell walls Heterotrophs Non-motile Unicellular (multicellular = moulds) Reproduce asexually (some also sexually) Some produce toxins Fungal Morphology -Yeast / Hyphae Typically around 3 μm Diameter 1 μm - 20 μm Fungal Morphology Multinucleated hyphae Septate hyphae Pseudohyphae Fungal Morphology http://www.medical-labs.net/ Life Cycle of Yeast  General Life Cycle of Filamentous Fungi Sexual spores (n) Germination (n) Asexual spore-producing (eg. Ascospores) structure forms (eg. Conidiophore) Sexual spore- containing structure forms (eg. Ascus) Asexual Asexual spores (n) Sexual Reproduction (eg. Conidiospores) Reproduction Mycelia (n) (2n) Mycelia fuse Germination (n) + - (n) (n) Asexual Spores Aspergillus fumigatus Sporangiospores Chlamydospores Zoospores Conidiospores Fungal cell wall Exact composition varies between species; Cell wall Galactomannan (Aspergillus, histoplasma) Call capsule GXM (Cryptococcus)  Fungal Cell Membrane - Sterol Cholesterol HO (mammals) Ergosterol (fungi) HO  Fungal Cell Membrane - Sterol 241 21 22 20 26 24 25 18 23 12 17 11 27 16 Stabilise the cell 13 D 19 C 1 9 14 15 2 10 8 membrane A B 3 5 7 HO 4 6 Essential component of Polar head groups Sterol stiffened region more fluid region cell in many organisms Phospholipid of cell membrane Required for stability Sterol and permeability of Phospholipid of cell membrane lipid membrane nm (approx) 3 2 1 0 Identification and Diagnosis Medical background – in-dwelling medical devices, lines, recent invasive surgery, drugs, environment Samples – Skin and nails, sputum, Bronchioalveolar Lavage (BAL), biopsies, CSF, blood. Specific antigen tests, ◦ β-1-3 D glucan – Candida, Apergillus, Pneumonocystis ◦ Galactomannan – Aspergillus, Histoplasma ◦ Specific PCR tests  Identification and Diagnosis Sensitivity – don’t miss cases, but can have a lot of false positives Specificity – no false positives, but can miss cases (false negatives). β-1-3 D glucan – good for detection of invasive infection. False positive if permeability of gut lining is high (neonates, bacterial sepsis), contaminated drugs, dialysis (nitrocellulose) Galactomannan – blood and sputum - good indicator of Invasive Aspergillus if patient is neutropenic (neutrophils quickly take up galactomannan). False positives from cereals and environment. Fungal infections can be difficult to positively identify - difficult to culture, need large sample volumes. Detection and Identification Culturing in enriched/selective media Macroscopic and microscopic examination, sometimes cannot culture - need microscopy Calcofluor white and fluorescence microscopy (chitin) Shyamala et al., JAMS, 2012, 2 p101 Fungi as Infectious Agents Some are just superficial – thrush, athlete’s foot Systemic diseases more serious – can be fatal 100,000s - only about 300 disease in animals In immunocompromised patients life threatening (and even in some healthy individuals) Fungal infection = mycosis (mycoses) Classification of Fungal Infections Morphology of causative agents ◦ Yeast ◦ Filamentous fungi ◦ Thermally dimorphic fungi Level of Invasion ◦ Cutaneous / superficial ◦ Subcutaneous ◦ Systemic Level of virulence ◦ Primary pathogens ◦ Dermatophytes (intermediate virulence) ◦ Secondary pathogens Classification of Fungal Infections Morphology of causative agents ◦ Yeast ◦ Filamentous fungi ◦ Thermally dimorphic fungi Level of Invasion ◦ Cutaneous / superficial ◦ Subcutaneous ◦ Systemic Level of virulence ◦ Primary pathogens ◦ Dermatophytes (intermediate virulence) ◦ Secondary pathogens Yeast Reproduce by budding and sporulation Some species can form hyphae and pseudopyhae under certain conditions (eg. Candida spp.) Smooth colonies in culture ◦ Candida albicans, C. tropicalis, C. glabrata, C. parapsillosis ◦ Pneumocystis jeroveci ◦ Cryptococcus neoformans Filamentous fungi Usually organised into hyphae Fuzzy colonies ◦ Aspergillus ◦ Fusarium ◦ Zygomyces ◦ Microsporum ◦ Trichophyton Thermally Dimorphic Fungi Can grow as either yeast or hyphae Primary pathogens – can infect healthy individuals Endemic to particular geographical regions Histoplasma capsulatum Blastomyces dermatitidis Coccidioides immitis, C. posadasii Paracoccidioides brasiliensis  Dimorphic Fungi - Lifecycle Natural habitat Animal host (Saprobic) Increased temperature (Parasitic) Mycelial phase Decreased O2 Yeast phase