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Medical Microbiology > 12. Fungal infections - current challenges > Flashcards

12. Fungal infections - current challenges Flashcards

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1
Q

Are fungal infections underappreciated?

A

Yes:
1. They have lots of cases
2. They create a large burden on healthcare
3. We are starting to see resistance to antifungals.
4. There are less drug in the 1st place due to the fact fungal cells are more similar to human cells.
5. They don’t receive a lot funding to research them.

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2
Q

Are fungi diverse?

A

Yes. They range from small yeast cells to edible mushrooms and poison.

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3
Q

Why do fungi associate with plants?

A
  1. Around 80% of plants are associated with fungi.
  2. Plants use fungi to help them take up nutrients like nitrogen and phosphorus.
  3. Plants cannot take these up by themselves, so they form a mutualistic relationship with fungi.
  4. The fungi take up the nutrients and pass them on to the plants. The fungi get glucose in return.
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4
Q

What are mycelia?

A

A complex underground network of the fungal filaments from the same fungi. They are like roots.

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5
Q

What fungi tend to have large economic value?

A

Truffles

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6
Q

What is Saccharomyces cerevisiae?

A
  1. A yeast that has been used as a model organism and helped many break throughs.
  2. Helped with Nobel prize winning science like cell cycle regulation.
  3. Used to make beer and bread
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7
Q

What do most microorganism pathogens not do?

A
  1. Kill the host
  2. It has no benefit for the pathogen if it kills the host as it dies too.
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8
Q

How are fungi different from most pathogens?

A
  1. It doesn’t care if it kills the host.
  2. Fungi release spores on death on the host so it survives.
  3. They will digest anything to get nutrients.
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9
Q

How do fungi obtain nutrients?

A
  1. They are saprophytic.
  2. They release enzymes that can digest anything around them.
  3. They will continue doing this even if it kills the organism they are infecting.
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10
Q

What is Geomyces destructans?

A
  1. A fungus that infects bats
  2. It wakes the bat up during hibernation.
  3. The bat goes to find food and dies because there is no food.
  4. This kills the bat and disseminates the fungal spores
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11
Q

What is Batrachochytrium dendrobatidis?

A
  1. A fungus that infects frogs
  2. Obligate aquatic fungi.
  3. Grows on the skin and prevents the frogs from breathing.
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12
Q

Why were fungi made their own kingdom?

A

They have similarities with other kingdoms but are distinct enough to be their own kingdom.

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13
Q

What similarities do fungi have with plants or animals?

A
  1. They have mitochondria.
  2. They have ATS ribosomes
  3. They can be multicellular and form tissues.
  4. Contain plastids
  5. Have genomes that are made of multiple linear chromosomes
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14
Q

What are the differences between fungi and other kingdoms?

A
  1. Chitin cell walls
  2. Ergosterol based cells membrane
  3. Filament cells called hyphae.
  4. Undergo sexual and asexual reproduction.
  5. Reproducing via spores.
  6. Heterotrophic
  7. Osmotrophic
  8. Chemoorganotroph
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15
Q

What makes a good fungal drug target?

A

the Ergosterol based cell membrane

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16
Q

Why do fungi switch from asexual to sexual reproduction?

A
  1. From environmental cues
  2. This included temperature or nutrients.
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17
Q

Why is fungi relationship with plants important?

A
  1. Fungi cannot produce their own food.
  2. This means they need to get sugar from plants and other organic matter.
  3. It also plays a key role in the nitrogen cycle and the recycling of nutrients
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18
Q

How do fungi aid soil production?

A
  1. They are osmotrophic, so they take up dissolved compounds in the soil.
  2. This also causes production of soil
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19
Q

How many fungal species are there?

A
  1. Over 5 million
  2. Around 600 species cause disease
  3. Only 200 fungi commonly cause infection
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20
Q

what kind of environments can fungi adapt to?

A
  1. They mostly live in the colder environment
  2. They can also survive and adapt to human body temperature, which is hotter
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21
Q

How many infections and deaths do fungal infections cause?

A
  1. a billion infections a year
  2. Kill over 1.6 million people a year (compared to 600,000 killed by breast cancer)
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22
Q

What is the profile of mortality of fungal infections?

A
  1. Bacterial infections infection a lot of people but don’t actually kill that many.
  2. Fungi kill a much larger percentage of the people they infect.
  3. Some fungal infection have 90% mortality and most have above 70%.
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23
Q

Who do fungi normally infect?

A
  1. vulnerable patients
  2. Diabetes
  3. Neutropenia
  4. Presence of another primary infection
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24
Q

What is the distribution of fungal infections?

A
  1. They are globally distributed.
  2. Mostly superficial infections
  3. Systemic and invasive infections are usually opportunistic
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25
Q

What normally causes superficial fungal infections?

A
  1. Caused by obligate pathogens and commensals
  2. Usually candida albicans, or trichophyton sp.
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26
Q

What normally causes subcutaneous fungal infections?

A
  1. Usually caused a traumatic implantation like surgery or skin breaks.
  2. Caused by Aspergillus terreus or madurella mycetomatis
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27
Q

What normally causes systemic fungal infection?

A
  1. Predominately opportunistic fungi
  2. caused by Aspergillus fumigatus, cryptococcus neoformans, C. albacians/auris
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28
Q

What is a primary pathogen?

A
  1. It causes infection in the setting of appropriate immune responses.
  2. Infection and damage even in a healthy host.
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29
Q

What is an opportunistic pathogen?

A
  1. These are associated with disease in people with impaired immune function.
  2. They almost never cause symptomatic or become clinically apparent in individuals with normal immunity.
  3. They take advantage of the immune impairment.
  4. They are commensals in healthy people but don’t cause infection.
30
Q

What is a virulence factor?

A

A component of a pathogen that damages the host.

31
Q

What is pathogenicity?

A

The capacity of a microbe to cause damage in a host.

32
Q

What is virulence?

A

The relative capacity of a microbe to cause damage in a host.

33
Q

What are Candida albicans?

A
  1. Unicellular, polymorphic fungus.
  2. Replicate by budding.
  3. Human commensal in oral and GI microbiome
  4. Obligate diploid that replicates using the parasexual cycle.
34
Q

What are the different morphological states of C. albicans?

A
  1. Yeast
  2. pseudo hyphae
  3. Hyphae
35
Q

What is the white/opaque switch in C. albicans?

A
  1. It is rare
  2. It is a requirement for the cell to be able to replicate by the parasexual cycle.
  3. It turns on different virulence genes.
36
Q

Why is the parasexual cycle needed in C. albicans?

A

To maintain genetic diversity

37
Q

What happens in the parasexual cycle in C. albicans?

A
  1. The cells normally have 2 mating types.
  2. The yeast randomly loses 1 of the mating types.
  3. If these single mating type cells undergo the white/opaque phenotypic switch they can replicate.
  4. This allows 2 cells of different mating types to fuse to create a tetraploid cell.
  5. This cell has 2 copies of each mating type so it randomly loses 2 of them. (normally by losing Chr 5)
  6. The creates a cell with a single mating type or with 2 different types
38
Q

What is candidosis?

A
  1. An infection caused by C. albicans
  2. Neutropenia is a risk factor.
  3. Candida switch to hyphae to become virulent. If this happens after phagocytosis it causes the cell to burst.
  4. If hyphae form extracellularly they cannot be phagocytosed and the host relies on neutrophil defence.
39
Q

What are ALS?

A
  1. A C. albicans adhesion protein
  2. They are a good target for the immune system to recognise.
  3. They can stick to biotic or abiotic surfaces.
  4. There are 8 different types which creates redundancy to avoid the immune system.
  5. ALS1 is associated with yeast state
  6. ALS3 is associated with hyphae state
40
Q

How do C. albicans cause damage to the host?

A
  1. Hydrolytic enzymes usually proteases to break down molecules to get nutrients.
  2. They move by paracytosis or transcytosis
  3. They break down e-cadherin junctions to move between cells
  4. SAP4 and SAP6 are associated with hyphae formation
41
Q

What is paracytosis?

A

moving within cells

42
Q

What is transcytosis?

A

moving between cells

43
Q

How do bacteria take advantage of C. albican infection?

A
  1. The fungi can break down E-cadhrin junctions and move between the cells.
  2. Some bacteria can stick to ALS on the fungi and hitch a ride between the cells.
  3. This is species specific mostly streptococcus
44
Q

Candidosis in systemic infections

A
  1. Not just blood stream but effective multiple organs
  2. Over 750,000 infections a year
  3. Mortality up to 75%
  4. Have treatments but resistance is rising.
  5. Risk factors are anything that impairs immunity: chemo, abdominal surgery, catheters, diabetes, and steroid use.
45
Q

What is Aspergillus fumigatus?

A
  1. The deadly mould
  2. very common and picked up easily
  3. No genetic recombination
  4. Can survive in a wide range of temperatures.
  5. Spores can enter the lower airways and cause infections and fungal balls.
  6. Present in decaying organic matter
46
Q

Why doesn’t fever help prevent Aspergillus infections?

A

They can survive a wide range of temperature so a small rise of body temp doesn’t effect them?

47
Q

What is the infectious lifecycle of A. fumigatus?

A
  1. The spores are in the air and are inhaled.
  2. They get into the lower airway
  3. The establish and embed in the airway.
  4. They disseminate in the lungs
  5. Forming of fungal balls.
  6. Dissemination to the brain
48
Q

What is Aspergillosis?

A
  1. Infection caused by Aspergillus fungi
  2. Over 200,000 infections a year
  3. Airborne spore
  4. Up to 95% mortality
  5. Diagnosis through microscopic examination
  6. Risk factors include: chemo, compost heaps and dry air conditioning units
49
Q

What are Mucoraceous moulds?

A
  1. Very common saprophytic fungi infecting plants.
  2. Also cause human infections globally.
  3. Found in jellies, syrups, leather, peanuts and cheese.
  4. Very, very fast growing
  5. Easily aerosolised
50
Q

why do Mucoraceous moulds cause serious infections?

A
  1. They grow very fast
  2. Go from a small and superficial infection to a massively invasive and destructive infection overnight
51
Q

What is Mucormycosis?

A
  1. Caused by Mucoraceous moulds
  2. Rare but lethal
  3. Very common in neutropenic patients
  4. They like diabetes patients due to the sugary blood.
  5. global distribution
  6. Rhinocerebral manifestation
52
Q

Why was there a problem with mucormycosis during the pandemic in India?

A
  1. Steroids are easily accessible and people were taking them to prevent covid infection.
  2. This doesn’t work but does increase the risk of fungal infections
  3. Lots of spores in the environment and caused mucormycosis
53
Q

What is cryptococcal meningitis?

A
  1. Over a million infections a year
  2. Caused by cryptococcus
  3. infection of the brain as it is attracted to the dopamine.
  4. Forms fungal balls in the brain
  5. An AIDS defining illness.
  6. up to 70% mortality
  7. Has non-specific symptoms so hard to spot and treat.
  8. No human to human transmission
54
Q

What are the 2 main groups of Cryptococcus species?

A
  1. C. neoformans
  2. C. gatti
55
Q

What are C. neoformans?

A
  1. Opportunistic pathogens
  2. Global distribution
56
Q

What are C. gatti?

A
  1. Primary and opportunistic pathogens
  2. Causes some very serious infections
  3. More localised to tropical areas
57
Q

What is Coccidioides immitis?

A
  1. Polymorphic primary pathogen
  2. Lives in soils and desert
  3. Endemic to SW US and Mexico
58
Q

What is the lifecycle of coccidioides immitis?

A
  1. At 25oC is exists at body temperature
  2. Once it enters a human and reaches body temp it switches to yeast cells
  3. Enters the parasitic cycle and produces spores
59
Q

What is Coccidiomycosis?

A
  1. Caused by coccidioides immitis
  2. Not many cases but a very high mortality
  3. mortality of up to 70%
  4. associated with physical labour
  5. Mostly in north america
  6. Generic symptoms
  7. Long term consequences
60
Q

What is candida auris?

A
  1. A new challenging fungal infection
  2. 1st identified in Japan in 2009
  3. Resistant to all 3 antifungal candida treatments we have
  4. Mostly a nosocomial infection
  5. found globally
61
Q

Candida auris in the UK

A
  1. First appeared around 2013-2015
  2. There were some outbreaks in hospitals in South England.
  3. Lots of different strains and they all are resistant to treatment
62
Q

What is Eumycotic mycetoma?

A
  1. Enters through a break in the skin
  2. Mainly present around the equator
  3. Mostly effects poor rural areas
  4. Produces lots of proteases and can break down bone.
  5. Surgery can be needed to remove he infection
63
Q

Mucosal candidiasis

A
  1. Oral thrush or thrush
  2. Vulvovaginal candidiasis
  3. Risk factors are reduced immune function, pregnancy, smoking, poorly fitted dentures, stress, diabetes and taking antibiotics
64
Q

Cutaneous candidiasis

A
  1. On the skin or embedded in the nails
  2. Risk factors: reduced immune function, uncontrolled diabetes, pregnancy, moist damp skin, and tight clothing
65
Q

What is Dermatophytosis?

A
  1. Infection of hair, skin or nails by keratinophilic dermatophytes
  2. Commonly caused by 3 genra: Microsporum, Epidermophyton and trichophyton
  3. Risk factors: pets, tight clothes, wrestling
  4. Found everywhere in soils, animals and humans, so you can easily pick up infections
66
Q

What is Trichophyton rubrum?

A
  1. Cause 75% of athletes foot
  2. Obligate human pathogen
  3. Increasing in incidence
  4. Normally there is host genetic predisposition
67
Q

Dermatophytosis: Tinea ungulum

A
  1. Nail infections
  2. Progressive and persistent
  3. Embeds into the keratin in the nail
68
Q

Dermatophytosis: Tinea capitis

A
  1. Scalp infection
  2. Normally a disease of poverty
  3. Avoid oiling hair or sharing combs
69
Q

Dermatophytosis: Tinea cruris

A
  1. Jock itch in the groin or perineum
  2. High humidity
  3. Prevention = loose cotton clothing, sterile towels
70
Q

What is ringworm?

A
  1. A superficial skin infection
  2. Common and easy to treat
  3. Can be caused from an animal vector
  4. Caused by T. rubrum
71
Q

What are the key points about fungal infections?

A
  1. Very few fungal species cause disease
  2. Fungal infections are either very common or rare and associated with high mortality.
  3. Severity of disease depends on host immune status

Medical Microbiology (16 decks)

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