Medical Mycology Lecture Notes PDF

MIMM211- Medical Mycology François Le Mauff, PhD (he/his) 1 Join at slido.com #3927771 ⓘ Start presenting to display the joining instructions on this slide....

MIMM211- Medical Mycology François Le Mauff, PhD (he/his) 1 Join at slido.com #3927771 ⓘ Start presenting to display the joining instructions on this slide. 2  INTOXICATIONS INFECTIONS 3 Photo by Yuris Alhumaydy & Olgo Kononenko on Unsplash  Lethal intoxications 4 Source: 9News Australia – August 6, 2023  The Angel death Amanita and Galerina sp. (Basidiomycota – Agaricomycetes) Both found in Quebec Contains cyclopeptide toxins – Amatoxins Heat stable, unaffected by drying. Responsible for almost all deaths from mushroom poisoning 0.1mg/kg = lethal dose (up to 15mg/cap) Inhibitor of RNA polymerase type II 5 Amanite phalloide (Credit : Archenzo) Psychoactive intoxications https://www.cbc.ca/news/canada/montreal/raid-magic-mushroom-montreal-police-1.6926814 6  Psylocybin & Psylocin Produced by numerous fungi Already used by many ancient civilizations: ie. Aztec – named them « teonanacatl » translating as “god’s flesh” Stoned Age theory 7 https://doi.org/10.1016/j.nrleng.2011.07.010  Psychoactive - Psilocybin Agonist at cortical serotonin 5-HT2A receptor Clinical trial to treat depression and PTSD 8 Credit: @NKWhiteman  Psychoactive intoxications The ergot fungus: Claviceps purpurea (Ascomycota – Sardoriomycete) Host: Rye 9 Picture credit: https://www.caymanchem.com/  Psychoactive intoxications Painting of Trial of George Jacobs, 1692 Host: Rye Artist: Matheson, 1885 10 Picture credit: https://www.caymanchem.com/ « Collateral » intoxications Napoleon Bonaparte, 1769-1821 11 Who killed Napoléon Ist? ⓘ Start presenting to display the poll results on this slide. 12 Scheele’s green bioremediation Ie: Scopulariopsis brevicaulis (Ascomycota – Sardoriomycete) Scheele’s green Trimethylarsine (Cupric arsenite) - Gosio’s disease 13  Secondary metabolites – Health benefits Canadian First nations use of fungi in traditional medicine Fomes fomentarius Bovista pila → Burnt on joints to treat arthritis → Spore used to prevent/stop nose bleeds Echinodontium tinctorium Amanita muscaria → Mixed with grease to make sunscreen → Concotion to make Eye-drop solution Haploporus odorus → Smoked to relieve headache And much more … Don’t try this at home! 14 doi.org/10.1139/cjb-2021-0052 Do NOT pick wild mushrooms, first nations have developed this traditional medicine over centuries. Summary – secondary metabolites Fungal secondary metabolites are an extremely diverse group of compounds Many exploited for commercial and medical applications A minority remain major health or economic concerns (ie. Aflatoxin) 15 We are constantly exposed to fungi 16 Globally, how many people are affected by fungal infections? ⓘ Start presenting to display the poll results on this slide. 17 Which disease kills more people yearly? ⓘ Start presenting to display the poll results on this slide. 18  Infections Superficial infections Invasive infections Most common infection & often benign Rare and lethal if untreated Frequent in immunocompetent Mostly in immunocompromising patients Example: Tinea corporis Aka. Ringworm Easily treatable Topical antifungal therapy Example: Mucormycosis Credit: James Heilman, MD 19  Superficial infections Provoked by dermatophytes (Tinea) – feed on keratin Tinea unguium Tinea pedis Ascomycota - Eurotiomycetes Commonest fungal infection of humans 5-10% population Up to 70% of all Difficult to eradicate Tinea 3-6 months oral Topical antifungal antifungals therapy for 10-14d Also called Recurrence common onychomycosis 20 https://doi.org/10.3390/pathogens11090957  Superficial infections Environmental origin: Anthropophile, Zoophile or Geophile 7yo female infected with Microsporum canis DOI: 10.15406/jdc.2018.04.00080 21  Superficial infections Candida albicans infections Credit: doi:10.1093/jmicro/dfs082 Human commensal organism (GI tract, mouth of most people, and vaginal flora) Morphological switch is required for virulence, and not completely understood today 22  Superficial infections Example of superficial infections: Candida albicans infections Oral thrush (oral candidiasis) Affect immunocompromised C. albicans diaper dermatitis Credit: doi:10.1093/jmicro/dfs082 Vaginal candidiasis (female) Balanitis (male) 23  Invasive infections Clinical classification: Yeasts Systemic disease, pulmonary disease absent or subclinical Main pathogens: Candida sp. & Cryptococcus sp. Molds Primary pulmonary disease with dissemination less common Main pathogens: Aspergillus fumigatus & Mucorales (ie. Rhizopus oryzae) Dimorphic fungi Primary pulmonary disease with dissemination prominent part of disease Pathogen examples: Histoplasma, Blastomyces … 24  Invasive infections - Yeast Candidemia C. albicans yeast reach the blood flow and access different organs Affect immunocompromised patients Fatal if untreated Average mortality rate: 20-50% Average stay at the hospital: 2-8 weeks 25 DOI: 10.1056/NEJMra1315399  Invasive infections - Yeast Cryptococcus sp. infections Basidiomycota Encapsulated yeast Two common sp.: C. neoformans & C. gattii Environment: Soil, Eucalyptus trees, Bird droppings. SEM micrograph credit: Jeehyun Karen You 26  Invasive infections - Yeast X-ray Tomography Cryptococcosis Acquired by breathing yeasts or spores Immunocompromised and immunocompetent at risk Pulmonary infections (cryptococcomas): - Often misdiagnosed - Asymptomatic in 25 to 50% cases All patients with this diagnosis needs to have a CSF puncture → Cryptococcal meningitis Culture Histopathology https://doi.org/10.3390/jof8111156 Diagnostic also require antigen test 27  Invasive infections - Yeast Cryptococcosis → Cryptococcal meningitis In HIV positive patient: 80% CSF culture are positive for Cryptococcus Treatment in 3 phases: Induction – 1 week under amphotericin B Consolidation – High dose of fluconazole doi:10.1038/nrmicro2522 Maintenance – Low dose fluconazole for a year Cryptococcosis overall mortality rate is above 50%, with a death toll estimate: 625,000/year 28 Where did Cryptococcus emerge as a pathogen of immunocompetent hosts? ⓘ Start presenting to display the poll results on this slide. 29 Invasive infections - Yeast: Cryptococcus infections 30 Invasive infections - Yeast: Cryptococcus infections Cryptococcus gatti >300 human >400 animal cases Appeared in 1999 Pneumonia and meningitis in immunocompetent patients Infecting native trees and soil 31  Invasive infections - Mold Majority of them are opportunistic, very aggressive and destructive Aspergillus most common (>80%) Aspergillus fumigatus most common species (Ascomycota) Disease: Invasive Pulmonary Aspergillosis Others Rhizopus, Absidia, Mucor (Zygomycetes) Penicilllium Pseudallescheria boydii 32  Aspergillus fumigatus 33 Source: https://www.youtube.com/watch?v=sbaWbiFt_Go&t=114s Conidia – Asexual spores We breath dozens of conidia everyday! In healthy individuals: Eliminated by the innate immune system and the mucociliary elevator Conidiophores 34  Aspergillus fumigatus In immunocompromised patients or patients with impaired lung functions A B C D Alveolar Infection E F G Aspergilloma Angioinvasion Flow F G H H Flow I J K L I J K L Lung propagation Invasive Pulmonary Aspergillosis Chronic aspergillosis (immunocompromised patients) (impaired lung functions) 35  Infection - Dimorpic Fungi (Endemic mycoses) Infect immunocompetent individuals Geographically restricted in range Classically dimorphic – environmental mycelium form vs infecting yeast form Histoplasma capsulatum Coccidioides immitis Paracoccidioides brasiliensis Blastomyces dermatiditis Penicillium marneffei 36 Dimorphic fungi – Blastomyces dermatidis 37  Dimorphic fungi - Blastomyces dermatidis Environment (25°C): Human body (37°C): Saprophytic mycelium Parasitic yeasts forming microconidia Lung infection Found associated with Dissemination to the wood – major dog blood and ultimately pathogen to other organs Endemic region: Great Lakes and Mississipi valley 38  Dimorphic fungi - Blastomyces dermatidis Cutaneous secondary infections are frequent Low mortality from Blastomycosis https://doi.org/10.1590/S0365-05962013000200022 39 Fungi are evolving with their environment … Next and last class: Mycology of a warming world, are we ready? 40