Fungi Flashcards
(96 cards)
1
Q
What do fungi feed on?
A
Dead plant or animal material in soil and compost heaps
2
Q
Name some similarities between the genomes of fungi and humans
A
Eukaryotes
Membrane-bound nucleus with several chromosomes
DNA contains introns
Plasma membrane and cytoplasmic organelles
3
Q
Name some differences between the genomes of fungi and humans
A
6000 genes
Normally haploid, only briefly diploid
4
Q
What is the structure of a fungal cell wall?
A
Cell wall of polysaccharides
Inner layer of chitin microfibrils (beta-1,4-NAG)
Outer layer of glucans (beta-1,3-linked glucose) and glycoproteins (asp-N-mannose or galactose, ser/thr-O-mannose or galactose)
5
Q
What are the three categories of fungal morphology?
A
Yeasts
Filamentous moulds
Dimorphic fungi
6
Q
Discuss yeasts: shape, growth
A
Oval or round
Unicellular
Mitotically divide by symmetrical binary fission or asymmetrical budding
Others grow as short cylinders called pseudohyphae
7
Q
How does Schizosaccharomyces pombe divide?
A
Symmetrical binary fission
8
Q
Discuss filamentous moulds: shape, growth
A
Hyphae - thin branching multicellular cylinder
Apical growth - mitosis at tip or t side branches behind the tip
9
Q
What are the different structures hyphae can make up, and give examples of fungi of each of these categories?
A
- Septate: interconnected compartments (Aspergillus)
- Aseptate: many nuclei in common cytoplasm (Mucor)
- Mycelium: many hyphae forming an interwoven mass when compacted together. Can form macroscopic structures (mushrooms)
10
Q
Dicuss dimorphic fungi
A
Fungi that are a different shape based on temperature
e.g. Histoplasma
Filamentous mould at 22 degrees in the environment
Yeast at 37 degrees in the body of a mammal
11
Q
What are spores?
A
Small, tough, light fungal cells adapted for dispersal to new habitats and/or survival in hostile environments
12
Q
What are the two states of differentiation of spores?
A
- Asexual/anamorph/mitotic/imperfect - yeasts produce internal endospores, moulds produce external endospores called conidia or internal spores inside a special hypha called a sporangium
- Sexual/telomorph/meiotic/perfect - motile gametes or specialised sexual hyphae. Means undergoes recombination and chromosome reassortment
13
Q
What are conidia?
A
Mould external endospores - asexual spores
14
Q
What is a sporangium?
A
A special hypha that some moulds form internal asexual spores in
15
Q
How do Deuteromycota replicate?
A
Asexually - incapable of sexual reproduction
16
Q
Where are sexual spores formed?
A
- Internally within tubular structure called an ascus
- Externally on specialised club-like structure called basidum
- Externally following fusion of specialised sexual hyphae
17
Q
Discuss Ascomycota - where are the spores formed, give examples of yeasts and moulds
A
Sexual spores in an ascus
Asexual spores in a conida
Yeast = schizosaccharomyes, saccharomyces, pneumocystis, candida
Moulds = asperfillus, fusarium, microsporum, trichophyton, epidermophyton
Dimorphic = histoplasma
18
Q
Discuss Basidomycota - where are the spores formed, give examples
A
Sexual spores on a basidum
Yeasts = Cryptococcus, malassezia
19
Q
Discuss Zygomycota - where are the spores formed, give examples
A
Sexual spores = external fusion of hyphae
Aseuxal = sporangium
Moulds = mucor, rhizopus
20
Q
Discuss Deuteromycota (imperfect fungi)
A
Only asexual - conidia
21
Q
Which 3 lifestyles do fungi use to get nutrition?
A
- Saprotrophs - feed on dead plant or animal material. Infect by accidental inhalation or implantation
- Parasites of living plants - diseases of crops mainly
- Parasites of humans - can cause disease
22
Q
How does an intact epithelium inhibit fungal entry?
A
- Physical barrier
- Secrete anti-microbial peptide
- Commensals inhibit multiplication of fungi on the surface
23
Q
Which PRRs recognise fungi?
A
- MBL mannose-rich structures
- Dectin-1 beta1,3glucan
- Dectin-2 mannan
- DC-SIGN mannose-rich structures
- Mincle Mannose-rich structures
- TLR2 - Phospholipomannan
- TLR4- O-linked mannose
- Mannose receptor N-linked mannose
24
Q
What does MBL recognise?
A
Mannose-rich structures
25
What does dectin1 recognise?
Beta1,3glucan
26
What does dectin2 recognise?
Mannan
27
What does DC-SIGN recognise?
mannose-rich structures
28
What does mincle recognise?
mannose-rich structures
29
What does TLR2 recognise?
Phospholipomannan
30
What does TLR4 recognise?
O-linked mannose (linked to a ser/thr)
31
What does the mannose receptor recognise?
N-linked mannose (linked to an asp)
32
Which PRRs activate the Syk pathway?
Dectin1
33
Which PRRs activate the Myd88 pathway?
TLR4
34
What are the key effector cytokines in response to fungi?
IL-17, IL-22
35
What is the pathway to activate proIL-1beta?
1. Dectin1 --> Syk --> Inflammasome NLRP3/ASC/Casp1 --> proIL-1beta to IL1beta
36
What are the pathways to activate NFkappaB?
1. Beta1,3-glucan --> Dectin2 --> Syk --> CARD9 --> MALT --> NFkappaB --> pro-IL1B + secrete IL6, IL23, IL12, TNFalpha
2. O-linked mannose -->TLR4 --> Myd88 --> NF-kappaB --> pro-IL1b, secrete IL6, IL23, IL12, TNFalpha
37
Which cytokines, secreted in response to NFkappaB, stimulate a Th17 response?
IL6, IL23
38
Which cytokines, secreted in response to NFkappaB, stimulate a Th1 response?
IL12 TNFalpha
39
Which conditions can cause impaired fungal sensing? What does this make you susceptible to?
Susceptible to superficial fungal infections
1. Dectin1 deficiency
2. CARD9 caspase recruitment domain-containing protein 9 mutation
40
What does impaired IL-17 receptor sensing do?
Susceptibility to chronic superficial Candida infection, or where auto-antibodies against IL-17 (or 22) inactivate the cytokines
41
What does impaired neutrophil number predispose to? When does this occur?
Deep fungal infections
Opportunistic filamentous moulds esp Aspergillus
Cytotoxic chemotherapy, chronic granulomatous disease where there is a mutation in one of the genes of the neutrophil NADPH oxidase system that normally generates superoxide needed to kill fungi after phagocytosis
42
What does impaired T cells and macrophage number or function predispose to? Why do people get this?
```
Yeast infection (superficial and deep) (candida, pneumocystitis, cryptococcus) and dimorphic fungi that can invade the body as yeasts (histoplasma)
Primary immunodeficiency syndromes, immunosuppressant drug reatment, haematological malignancies, AIDS
```
43
How do you diagnose a fungal infection?
1. Culture of fungus from clinical sample e.g blood, urine, skin scraping, lung biopsy
2. Detection of fungal polysaccharide or fungal DNA in a sample e.g Cryptococcal polysaccharide in blood or CSF, pneumocystitis DNA in lung fluid
3. Tissue biopsy for microscopy and culture - morphology to ID moulds
44
Amphotericin, nystatin
Polyene
| Inhibit ergosterol function
45
Clotrimazole, fluconazole, voriconazole
Azoles
| Inhibit ergosterol synthesis
46
Terbinafine
Allylamine
| Inhibit ergosterol synthesis
47
Grisofulvin
Inhibit fungal microtubule synthesis
48
Caspofungin
Echinocandin
| Inhibits beta-1,3-glucan synthesis of the fungal cell wall
49
What is ergotamine?
A fungal toxin in rye crops
| Potent vasoconstrictor that causes painful ischaemia/gangrene of fingers and toes
50
Where are filamentous moulds commensal?
NOWHERE
51
What is ringworm?
Superficial fungal infection of dead keratinised tissues (skin, nails, hair)
52
What are dermatophyte moulds?
Microsporum, trichophyton, epidermophyton (all cause athlete's foot)
Very common in humans, wild and domestic animals
Acquired by spores: direct person-to-person contact, indirect sharing contaminated clothing or environment
Not life threatening, don't invade into deeper tissues
Chronic
Induce local type IV sensitivity (host CD4+ T) so increased skin proliferation --> flaky, scaly skin + itching, leading to scratching and secondary bacterial infection
Hard to eradicate, may recur
53
What does candida albicans cause superficially?
Disfiguring chronic fingernail condition
54
What does Malassezia furfur cause?
Pityriasis versicolor (blothy skin rash that doesn't tan)
55
What is rose picker's disease?
Subcutaneous fungal infection
Invades as a yeast at 37 degrees
Forms chronic skin nodules that may spread up the arm
56
What are the different levels of fungal infection?
1. Toxins
2. Commensals overgrowing
3. Superficial
4. Subcutaneous
5. Systemic
57
What are the two main types of systemic fungal infections?
Systemic pathogens and systemic opportunists
58
How do histoplasma change morphology?
Temperature-sensitive dimorphism regulating kinases DRK1 and RYP1 induce a pattern of gene expression:
- Expression of alpha-1,3-glucan not recognised by host PRRs
- Fungal hsp60 which binds to CD11/CD18 on the surface of human mphages
- Secreted protease-resistant calcium binding protein that facilitates fungal growth within macrophage vacuoles
59
What are the temperature-sensitive dimorphism regulating kinases called?
DRK1 and RYP1
60
How are fungal infections controlled?
T cell response --> mphages --> granulomas
61
How do you identify if people have a memory T cell response against Histoplasma?
Skin test- inject dead histoplasma antigen into the skin
62
How does histoplasma enter the body?
Lung (accidentally breathed in)
Soil and bat droppings in Mississippi and Ohio valleys
Inhaled by bats
63
Name the forms of histoplasmosis, the clinical features, and the final outcome
Asymptomatic: positive skin test only, resolution
Acute pulmonary (influenza-like): lung infiltrates, enlarged hilar lymph nodes, resolution
Chronic pulmonary: chronic lung inflammation, fibrosis, cavitation, progressive incapacity
Disseminated (spread through blood): focal spread outside lung or widespread disease (skin, larynx, adrenal), often fatal
64
Which host defects can predispose to systemic opportunist fungal infection?
Defect in skin barrier (IV, burns)
Neuropenia (leukaemia or its treatment)
Reduced function of neutrophils (chronic granulomatous disease)
Reduced number/function of T cells - lymphoma, AIDS, immunosuppressive drug treatment
NOT LACK OF AB
65
What is the receptor on dendritic cells used to recognise histoplasma?
VLA-5 fibronectin and fibrinogen receptor
66
What type of response is the histoplasma response?
Th1
67
How does candida divide?
Divide by asymmetrical budding
68
What is the structure of candida?
Commensal yeast on moist mucosal surfaces
Some strains have increased capacity for adhesion and invasion through the epithelial surface by forming pseudohyphae
Forms a biofilm: large communities of organisms embedded in a sticky extracellular matrix at the interface between a liquid medium and a sticky extracellular matrix
69
Where do you find candida?
Throat, gut, vagina
70
What is candidalysin?
A secreted 31 aa peptide toxin that damages epithelial cells
71
When does oral candidiasis occur?
Newborn babies, following inhaled steroid treatment for asthma, following antibiotics
72
When does vulvo-vaginitis candidiasis occur?
Pregnancy, following antibiotic treatment, nappy rash
73
When does UTI candidiasis occur?
Following urethral catheter and/or previous antibiotic treatment
74
When does oesophageal candidiasis occur?
Advanced HIV, organ transplant
75
When does candidaemia occur?
Bloodstream infection
| IV cannula in hospital, IV drug users, endotracheal tube
76
When does disseminated infection of candida occur?
Spreads through blood to eyes, liver and spleen, heart valves
Mainly in immunosuppressed people
77
How do you treat candida?
Fluconazole or caspofungin
78
Name a species of candida resistant to fluconazole
Candida krusei
79
How is pneumocystitis jirovecci transmitted?
Human-to-human by inhalation, obligate intracellular parasite
80
Are recurrences of pneumocystitis jirovecci due to re-activation or re-acquisition when individuals have impaired T cell immunity?
Re-acquisition.
81
What does pneumocystitis jirovecii cause? e.g. pathophysiology, signs, symptoms
Diffuse inflammation of lung alveoli
Clusters of oval fungal organisms in the alveolar airspaces, injury to alveolar epithelial cells, alveoli filled with protein-rich foamy exudate
Impairs gas exchange so arterial hypoxaemia worst during exercise
Dry cough, progressive breathlessless, fever, weight loss
X-ray widespread hazy opacification
82
Treament of pneumocystitis jirovecii?
Co-trimoxazole - inhibits fungal folic acid synthesis +
| Prednisolone = inhibit innate inflammatory response to fungal polysaccharides released by dying organisms
83
How does pneumocystitis jirovecii replicate?
Trophic form = binary fission
| Sexual form = sexual spore/cyst, after maturation the collapsed spore releases trophic forms
84
How do you prevent pneumocystis pneumonia in high-risk immunocompromised patients?
Regular low dose treatment with co-trimoxazole or inhaled pentamide
85
Pentamide
Used to prevent pneumocystis pneumonia in high-risk immunocompromised patients
Inhibits topoisomerase enzymes in mitochondria
86
How do humans acquire Cryptococcus neoformans?
Inhalation of bird droppings, then spreads through lung to CNS
87
What is a key virulence factor of Cryptococcus neoformans?
Thick polysaccharide caspule
88
Are the types of infection of Cryptococcus neoformans?
Pneumonia rarely, meningo-encephalitis when T cell immunodeficiency
89
What does Cryptococcus infection cause?
```
Slowly worsening meningo-encephalitis
Progressively worsening headache
Fever
Confusion
Hydrocephalus
Coma
20% fatality
Survivors may have persistent neurological disability including blindness
```
90
How do you treat Cryptococcus?
Amphotericin + flucytosine, then high dose fluconazole long term
91
Amphotericin
Polyene antifungal and antiparasitic, forms pores in the membrane by an ergosterol-dependent mechanism. Drug of choice for most systemic mycoses: Cryptococcus, candida, aspergillus. Also antiprotozoal
92
How is aspergillus fumigatus acquired?
Air-borne spores
Inhaled
Mouldy hay, compost heaps, hospital re-building work
93
What types of infection does aspergillus cause and under which conditions?
Airway colonisation - asthma
Aspergilloma (localised mass of hyphae) - pre-existing lung cavity e.g. after prev TB
Invasive infection of lung or paranasal sinuses - severe neutropenia e.g. after chemotherapy for leukaemia
V high fatality
94
Treatment for aspergillus?
Amphotericin or voriconazole, surgery if poss
95
How do you get mucormycosis?
Inhalation of spores
Direct contamination of wounds (tornado or tsunami)
Invades aggressively through paranasal sinuses or lungs
96
How do you treat mucormycosis?
Urgent surgery to remove dead tissue + IV amphotericin
