Fungi Flashcards
Discovery of Pencilin
1928 London, UK
by Sir Alexander Fleming
first antibiotic isolated from fungi
Mucormycosis
毛霉病
Caused by Rhizopus oryzae.
Highly drug résistent
Good side of fungi
1.Pharmacential industry
-Antibiotics
-Other pharmacential (ie. Statins)
- Food industry
-Mushrooms
-Yeast for baking, fermentation (car, kimchi泡菜)
-Cheese
-Enzymes and chemicals (ie. Citric acid for soft drinks)
3.Absorb nuclear radiation
- Break down plastic pollution
-Biodegradation: fungi can decompose all organic material and even plastics but also lumbers木材, building materials, food, us
Bad side of fungi
- Infection
-Invasive and superficial mycoses. - Intoxication
-Aflatoxicosis, ergot alkaloid , toxic mushrooms
-Toxic building syndrome 病态建筑综合症，长期在特定建筑内出现与该环境相关的症状 - Allergy: Asthma 哮喘，Siusitis鼻炎等
Fungus is a mostly unknown kingdom
Uncertain mumber: 1.5-12 millions, only 150,000 species identified
Discovery rate: 1000 - 2000 species /year
Characteristics of fungi
Eukaryotes
Cell wall
Heterotrophy
Unicellular
Asexual and sexual reproduction
Eukaryotes
-True nucleus
-Protein secretory pathway (ER , Golgi)
-Mitochondrion (like animal)
-Vacuole (like plant)
-Cytoplasmic membrane contain Ergosterol (animals heve cholesterol, plants have mix of sterol)
Cell wall of fungi
exoskeleton of fungi
Function: structure, protection, exchange
Made of mostly polysaccharides and chitin -polysaccharides differs among species
-all species share same chitn (polymer of beta-1, 4 GlcNAc)
Heterotrophy
absorb nutrients from envrionment, no vascular system
Saprotroph
Symbiont
Parasite
Predators
Unicellular
1.Yeast = single cell, 1 nucleus
-reproduction by budding or fission
-environmental signals can initiate yeast transition to hyphae or pseudohyphae
2.Mold: filamentous tubular structure, multiple nuclei hyphae can contain septa
-septated hyphae: separate hyphae into smaller sections
-aseptated hyphae
-Mycelium: ensemble of hyphae
Asexual and sexual reproduction
1.No sex
-Asexual form called Anamorph, reproduce by mitosis
2.Sex
-sexual form called Teleomorph, reproduce by meiosis
-2 main type
3.Parasexual
Gene recombination through mitosis
Advantages of asexual reproduction
don’t t need a partner
maintain valuable genetic combination
2 main type of sexual reproduction
1.Heterothallic
Sex with other mating type
2.Homothallic
sex with same mating type (can be same thallus菌体)
Taxonomy of fungi
phylum – mycota
sub phylum – mycotina
class - mycetes
3 main groups of fungi
zoosporic fungi: most primitive
zygomycetous fungi
Dikarya subkingdom: most recent
Zoosporic fungi
primitive aquatic fungi
parasite / Symbiont / Saprotroph. (most parasite, kill the host)
anchored via rhizoid structure
Spread via zoospores (asexual), swim through their zoospores
Zygomycetous fungi
adaptation to life on land. (First fingi)
Saprotroph
Aseptated filamentous fungi
Spread via zygospores (sex) / sporangiospores (asexual)
Dikarya
2 groups:
Ascomycota (sac fungì)
Basidiomycota (little pedestal fungi)
Ascomycota
filamentous fungi or yeast (septated)
spread via ascospores(sex) and conidia(asexual)
Basidiomycota
septated filamentous fungi or yeast
spread via basidiospores (mostly sexual)
Spread strategies of fungi
1.wind
2.modify animal behavior & sex life
3.shoot spores as far as possible.
4.call up for some animal help and take a ride
Spread-Attracting animals
Ex. Stinkhorn fungus Phallus impudicus
-Fruiting body emerges with tremendous force
-3 mushrooms can lift 400 kg
-Produce sticky spore mass that smells like rotting meat
-Attract insects who carry away the spores
Spread-Controlling Animal
Ex. Massospora cicadina
-colonize the body of cicadas, replace their subdomain where the reprodutive organ locate
-Let the male behave live a female: land on leaf, shakng wings make sounds to attract male, and the attracted male is tend to get infected and spread it out
Spread-Mastering the wind
Basidiospore formation
1.Plasmogamy: mycelia form (1n) two mating type (+ /-)
2. + and - fuse, form a dikaryotic mycelium
3. Mitosis: basidiocarp forms, gills of the basidiocarp contain basidia
4.Karyogamy: basidia form diploid nuclei—zygote (2n)
5.Meiosis: 4 haploid nuclei are formed in the basidium (1n)
6.Cell division: 4 basidiospores are formed
7.Dispersal and germination of basidiospores
-Basiodiomycetes can produce of over a billion of spore/day
-Basiodiomycetes form complex fruiting bodies that produce basidiospores. (Increase dispersion by increasing surface area and elevation)
-Gills, Pores, Folds: increase Surface area
Basidiospore release
-apiculus secrete Buller’s drop
-When Buller’s drop contact with the water layer on the top of the spore, they mix together and the surface tension catapults the spores away from the sterigma
-This ensure the spore falling out without smashing the gill
-The water accumulate under the fungi: evaporation cools the air up to 5摄氏度 less the cold air is heavier, when it got warm up, is go up and create an air convection cell taking away the spores cm~ Km away
Spread-going with wind
Ex. Ascomycetes
- Plasmogamy: Mycelia—>ascogonium and antheridium fuse
- Mitosis and cell division: formation of many dikaryotic hyphae, form a fruit body called ascocarp, ascus(asci) form at the tips of hyphae
- Karyogamy: Nuclei in the asci fuse to form a diploid zygote (2n)
- Meiosis: an ascus with 4 haploid nuclei is formed
- Mitosis and cell division: 8 haploid ascospores are formed
- Dispersal and germination
Asexual cycle: mycelia—>mitosis: spores—>germination—>mycelia
3 different types of ascocarp
1.Apothecium
Shotgun
Cup fungi
2.Perithecium
Rifle
Flask fungi
3.Cleistothecium
Grenade
Release all at the same time
Spread-fungi does not need wind
Ex. Pilobulus sp.(zygomycetous fungi)
Sexual reproduction:
1.spores germinate to 2 mating types, when grow close enough, extension of mycelia (1n) called gametangia form between them
2.Plasmogamy: fusion between +/- mating types result in a zygosporangium(form a thick protective coat) with multiple haploid nuclei
3.Karyogamy: Nuclei fuse to form a zygote(2n) with multiple nuclei
4.Meiosis and Germination: a sporangium(1n, haploid spores form inside) grows on a short stalk
5.Germination
Asexual reproduction: spores—>mitosis—>mycelia—>germination
Consequence of fungi spread
Might wipe out a entire species from earth
Hypothesis: fungi and dinosaur
Fungi might contribute to the extinction of the dinosaurs
since they cannot grow under 37 degree, mammal survival
Mass extinction event targeting amphibians
fungi
How to kill
Situation now
Bd & Bsal: Chytrids belongs to zoosporic fungi
Amphibians are killed by disrupting the skin functions, leading to cardiac arrest
Animal trade disseminated(传播) the chytrids on all continents.
Close to 100 species already extinct.
2nd most dangerous species for biodiversity
Dutch elm disease
Fungi (3 main species)
How
Symptom
Situation in Montreal
Blue stain fungus carried by a beetle
Beetles make holes on pine trees and infect the fungi in the tree.
3 main species of blue stain fungus affect pine trees: (Ascomycota - Sardoriomycetes)
-Grosmannia clavigera
-Ophiostoma montium
-Leptographium longiclavatum
Fungi colonize the tree phloem and feed on the sap, leading to pine tree death
In Montreal Rhytima sp.
• 60,000 trees replanted (Norway maples: faster growing with yellow leaves)
• Norway maples are very susceptible to tar spot.
• Native sugar maples are relatively resistant
White nose syndrome on bat
Pathogen: Pseudogymnoascus destructans (Ascomycota)
-Saprotroph
-Loves cold temperatures
Mortality: 5 million/year
70–100% of bats infected will die because of metabolism shutdown
As temperatures rise, immune system controls the infection, 但是下次冬眠会感染更多，一直循环消耗，直到bats在冬眠结束前死亡
white nose syndrome in bat 地域差异
In Europe: No mass mortality
A mycovirus uniquely found in North American Pd isolates.
Viruses infect fungi: RNA in fungi encodes virus enzymes:
-Some increase the virulence e.g., Pd
-Some decrease the virulence e.g., Aspergillus fumigatus a human pathogen), it let fungi survive longer.
In the early 2000s, Europeans brought Pd & mycovirus to caves in New York State.
Impact of the white nose syndrome in bat
-
Pollination
More than 300 fruit trees depend on bats for pollination -
Insect population control (bats feed on insects):
-Saves money spent removing bugs ($4 billion/year)
-Reduces the abuse of insecticides.
Banana
Herbs
-Half of the banana is difficult to obtain through fertilization (seed is too big)
-Selected those that don’t require fertilization and spread them everywhere
Big Mike (Gros Michel)
Disease, place, fungi, habitat, how to kill plant
Tasty
conquered the world
Fusarium oxysporum TR1
Ascomycota – Sardoriomycete
1874 - Australia: Banana farm decimated大量毁灭 by fungal disease
Fusarium:
-lives in the soil
-their spores sense plant growth (via materials secreted by roots)
-Spores germinate, invade plant roots, grow in xylem, and lead to the plant lose their water supply, fungi will clog the vessels and this cause plant death
-fungi sexual/asexual reproduction
-spore left in soil
Cavendish (Vive Cavendish)
Less tasty, less long-lasting
History repeats with Fusarium oxysporum TR4
The problem of monoculture and fungal infection
- The only solution is to use anti-fungal, but: Antifungals create resistance, and we use antifungals to treat ourselves
- Gene editing is not a complete solution (other strains might infect in the future+Global trade)
Wheat Rust
Pathogen, life cycle, and framer’s response
Pathogen: Puccinia graminis Basidiomycota
-In the summer, P. graminis reproduces asexually in wheat, growing fast and spreading spores via wind
-In winter, they switch hosts to barberry plants and reproduce sexually
-when temperature rise, switch back to wheat
Farmers’ Response
-Removed barberry plants → Wheat rust disappeared for nearly 60 years
-Later, to protect barberry carpet (moths), black barberry plants were restored → Wheat rust returned
Mycorrhizal
What relationship, how long, what fungi
Symbiotic relationship between plants and fungi.
Present for 450 million years and found in 80% of plants.
Fungi: mainly Glomeromycotina (Zygomycetes)
4 Types of Mycorrhizal Interactions
- Arbuscular.
- Ectomycorrhizae
- Orchid → seeds can’t germinate without fungi
- Ericoid
General advantage of mycorrhizae
With mycorrhizal fungi, roots can cover more soil to get nutrients.
2 Main Groups of Mycorrhizal Interactions
- Arbuscular Mycorrhizae Fungi (AMF)
- Ectomycorrhizae
Benefits of Mycorrhizal Fungi
3 big point
What can fungi improve in soil
- Zone of exchange between plants and fungi
-Fungi improve water and nutrient assimilation (e.g., N, P…)
Ex. Plants can’t take phosphate on their own, they need fungi to take it for them
-Plants provide carbon (carbohydrates, lipids) to fungi - Improved soil quality
-Fungi secrete glomalin (hydrophobic glycoprotein), which interact with particles in soil and start to organize it in macroaggregate
Fungi can improve:
-Soil structure
-Carbon sequestration.
-Water flow and availability
-Biodiversity
-Heavy metal absorption
A richer soil can support more life
- Stimulate plant immune defense
-sometimes plant consider fungi as a “pathogen attack,” triggering immune responses
-Benefits: - Pathogen presence prevention
- Stimulation of the plant general health/metabolic activity (defense)—ISR (induced systemic resistance)
Harnessing利用 mycorrhizal fungi enables more sustainable agriculture
Botrytis cinerea
What
Good/bad side
gray mold
Ascomycota, leotiomycets
Bad Side
-Causes ~$10 billion/year crop losses.
Good Side
-“Noble Rot” → Sauternes
-Ideal growth conditions in France plant farm: Cool, moist in the morning; warm in the afternoon
3 grape varieties
- Semillon → main grapes used with thin skin grapes
- Sauvignon Blanc → bring acidity to the wine
- Muscadelle → Grapes with floral note easily infected by fungi
Infection process of Botrytis cinerea
- Fungi land on the top of grapes and grow germ tubes (Appressorium) destroy the first layer of cells in epidermis
- Hyphae grow, penetrates the grape, starting infection
- Grape skin bursts as fungi grow, creating holes, water evaporates, give a sweet flavor
- Hand pick harvest of the grape with noble rot with correct maturation degree
fungi for cheese production
Penicillium roqueforti (Ascomycota - Eurotiomycetes)
Recent fungi with long tubes septated
Proteolysis of dairy protein and lipids, secretion of flavorful secondary metabolites
Blue cheese–What is the blue
What reproduction method
How to make better cheese
Blue comes from the spores of the fungi
Spore is made through asexual reproduction
To make better cheese: force penicillin do sexual reproduction to recombine DNA
The angel death
Fungi: Amanita phalloide (Basidiomycota)
-Produces amatoxins: cyclopeptide toxins, which is heat stable and unaffected by drying
-Lethal dose: 0.1 mg/kg (up to 15 mg/ a mushroom cap)
-Inhibits RNA polymerase II
-Responsible for most mushroom poisoning deaths
Magic mushroom
Related hypothesis
Clinical use of
Fungi: Psilocybin & Psilocin
-Alters the way of the perceive of reality
-Used in ancient civilizations (e.g., Aztecs).
“Stone Age Theory”: Brain size increases linked to mushroom use.
Highly criticized
Psilocybin agonist at cortical serotonin 5-HT2A receptor, they are used in clinical for depression and PTSD
Ergot fungi
Claviceps purpurea - Ascomycota, Sordariomycete
-Host: rye
-Reaction: lysergic acid(psychoactive drug) +diethylamine=LSD
Injection with Rye with fungal infection—> the witches trial in middle age
Fungi: Scopulariopsis brevicaulis
Ascomycota - Sordoriomycete
-Scheele’s green + growth of S. brevicaulis → releases As (arsenic) to the air
-product of this reaction is trimethylarsine which cause Gosio’s disease
health benefits of secondary metabolites of fungi
Many fungi secondary metabolites exploited for commercial and medical applications, only a minority remain major health or economic concerns (ex. Aflatoxin)
Tomes fomentarius: Burnt on joints to treat arthritis (药膏).
Echionodontium tinctorium: Mixed with grease to make sunscreen.
Haploporus odorus: Smoke used to relieve headaches.
Bovista pila: Spore used to prevent/stop nosebleeds.
Amanita muscaria: Concoction used to make eye-drop solutions.
Fungi infection overview
80% of the population will be affected once across their life by fungi.
Some infections cause severe diseases.
Superficial infection
Most common infection and often benign
Frequent in immunocompetent 正常免疫者
Provoked by dermatophytes (Tinea) 皮肤真菌, feed on keratin
Invasive infections
Rare but fatal if untreated.
Mostly in immunocompromising patients (免疫障碍病人).
Example: Mucormycosis (严重致命性菌病)
Tinea corporis
ring worm
easy to treat, only need topical antifungal therapy
Tinea unguium
-5-10% population
-Difficult to eradicate (难以根除)
-3-6 months oral antifungal
-Also called onychomycosis (甲真菌病)
Tinea pedis
Commonest fungal infection of humans
Up to 70% of all Tinea
Topical antifungal therapy for 10-14 days
Recurrence common
Feed on skin
Candida albicans infection
Type of infection
Relationship with human
What disease
Superficial infection
3 different forms
Yeast form → pseudohyphae → true hyphae (causes disease)
Commensal with humans (GI tract, mouth, vaginal flora)
Morphological switch is required for virulence (not completely understood)
Examples of disease:
Oral thrush, diaper dermatitis, vaginal candidiasis, balanitis
Clinical classification of fungi infection
- Yeasts
-Systematic disease, pulmonary disease, absent or subclinical
-Have little or no clinical symptoms. - Molds
-Primary pulmonary disease with dissemination (传播)
-rarely spreads to the whole body - Dimorphic fungi
-Primary pulmonary disease with dissemination as the prominent part of disease
-Can convert to hyphae forme, spread in the body
Candidemia albicans (白色念珠菌)
Type of fungi, type of infection
Infect who, where
Yeast
Invasive infection
-从缺口go into blood, and go to different organs
-Affects immunocompromised patients.
-Fatal if untreated; even if treated, mortality is 20–50%
-Average stay at hospital: 2–8 weeks.
Cryptococcus sp.
Type of infection
Structure
Yeast
Invasive infection
Basidiomycota
Encapsulated
an rigid & dense outer layer of sugar
protects cell wall, a massive virulence factor
2 main species of Cryptococcus sp.
Living environment
C. neoformans & C. gattii.
Living environment:
soil
Eucalyptus trees
bird droppings
Infection way & disease & treatment of Crytococcus sp.
Acquired by breathing yeast or spores
Pulmonary infections
-often misdiagnosed as cancer
-Asymptomatic in 25-50% of cases.
-Patients with diagnosis need to do a CSF puncture because Cryptococcus loves to go into your brain and cause cryptococcal meningitis
(macrophage engulfs yeast; macrophage goes through the BBB; yeast can be released into the brain)
HIV+ patients: 80% CSF culture are positive for Cryptococcus
Treatment: 3 phases:
-Induction: 1 week under amphotericin B
-Consolidation: high dose of fluconazole
-Maintenance: low dose of fluconazole for a year
Example:
Cryptococcus gattii (appeared in1999)
-homothallic reproduction
-cause pneumonia, and meningitis in immunocompetent patients
-infecting native trees and soil
Mold invasive infection
Feature, infection place
Most common fungi
Infection in lungs, rarely disseminating.
Majority are opportunistic, very aggressive, and destructive.
Aspergillus most common (>80%):
-Aspergillus fumigatus most common species (Ascomycota)
-Cause invasive pulmonary aspergillosis
Other species:
-Zygomycetes: Rhizopus, Absidia, Mucor
-Penicillium
-Pseudallescheria boydii
Aspergillus fumigatus
Structure, infection, type of disease
Conidiophores → Conidia (asexual spores)
Healthy individuals: eliminated by the innate immune system and the mucociliary elevator.
For immunocompromised patients: pathogen goes to alveolar and then blood vessel → lung
Cause:
1. Invasive Pulmonary Aspergillosis
2. Chronic Aspergillosis: If you have impaired lung function, stays at the impaired place and grows.
Dimorphic Fungi infection
Endemic mycoses: 地方性真菌病
Infection type switch in the middle
Infect immunocompetent individuals
Geographically restricted in range
Environmental mycelium form vs. infecting yeast form
Blastomyces dermatitidis
Dimorphic fungi infection
Environment (25°C):
-saprophytic mycelium forming microconidia found in wood; a major dog pathogen
-Endemic region: Great Lakes and Mississippi Valley.
Human body (37°C):
-parasitic yeast
-Lung infection → dissemination to blood and other organs
-Cutaneous 皮肤的 secondary infections are frequent —>grow into mold
Low Mortality
Problem of antifungal
limited because we are both eukaryotes, maybe toxic to us
Targets of fungi
- Cytoplasmic membrane → ergosterol
- Cell wall
Target Cell wall
What, why not chitin
What drug
β-1,3-glucan
Chitin: Will also affect insects and shellfish
Echinocandins: cell wall inhibitors
-Newest family of molecules approved by the FDA (2001)
-Fungicidal to yeast: kill
-Fungistatic to mold: stop growth
Example: caspofungin
Target ergosterol Overview
Ergosterol: ensures fungal plasma membrane fluidity
Two families of antifungal drugs targeting ergosterol:
-Polyenes
-Azoles
Polyenes
1950s
Ergosterol binder
Makes holes in the membrane.
Only used in severe cases of invasive infection
Important toxicity:
Maximum dose: 1 mg/kg/day over 2-4 hours.
Cholesterol & ergosterol (structural similarity)
Example: Amphotericin B
Azoles
1960s
Inhibitor of ergosterol synthesis
2 types of structures:
-Contain imidazole group (2 N)
-Contain triazole group (3 N)
Fungicidal: mold infection (invasive)
Fungistatic: yeast
Antifungal resistance
For all drugs, the resistance relate is increasing
Agricultural use of azoles:
- A driving source of resistance.
- 14% of environmental Aspergillus strains resistant to azoles in the UK
- 7% of spores found in Eastern Himalayas are resistant to at least 1 medical azole
Biofilms
Can increase resistance to a drug by 1,000-fold.
Self-made matrix constituted of polysaccharides and proteins
Functions:
-Protect fungi from the environment
-Blocks immune cells: can’t reach the fungi with the sugar outside their hyphae
New antifungal and situation now
New molecules are in preclinical and clinical stages
Repeats of same mistakes are in perspective
Ipflufenoquin
-Approved by US EPA 2023
-Able to select for resistant strains in the field, even though we haven’t actually started to use it in clinical settings
Main concerns about fungi
- Losing antifungals
- More people at risk (more immunosuppressed people)
- Temperature rising:
-Now only 6% of fungi can grow at 37°C today, but what about tomorrow? - Having to deal with new conditions helping fungal dispersion and disease.
WHO Fungal Priority Pathogens List
• Critical Group
• High Group
• Medium Group
Candida auris
Which group
Critical group
-90% resistant to at least 1 antifungal.
-30% resistant to at least 2 antifungals.
-4% resistant to everything (pan-resistance).
-Fast spread all around the world.
-Mysterious origin: 4 clades suddenly appeared around the world in 5 years. They are not from the same ancestor
Hypothesis of the spread of candida auris
- Global warming:
Allows strain to resist temperatures up to 42°C. - Ecological niche:
-Rich in salt (resistance up to 10% NaCl)
-Rich in antibiotics
-Persistence facilitated on plastic pollutants. - Intermediate animal reservoir remains to be established
-also climate change might lead to habitat shift, transmit the fungi pathogen in more regions
More superbugs are coming
Ex. Trichophyton indotineae
全球扩散
Coccidioides spp.
Medium group
Dimorphic fungi:
Coccidioides immitis and Coccidioides posadasii.
Cause Valley Fever
-Pulmonary: pneumonia-like symptoms
-Dissemination to the skin, lymph nodes, bones, joints, and CNS
-40% of people inhaling spores become symptomatic, 1–5% experience dissemination.
Spread to region with low humidity and high temp.
-climate change increase its range
Result of climate change
More unexpected pathogen appear to affect human
