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Microbiota On Mucosal > C6- Cryptococcus Virulence > Flashcards

C6- Cryptococcus Virulence Flashcards

1
Q

Where can you find it (saprophytic)

A

Avian habitats in cities
Soil
Trees eg eucalytpus

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2
Q

How do they usually reproduce (not dimorphic yeast)

A

through yeast budding

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3
Q

What mating type are 95% of haploid yeast (clones through asexual budding just fine )

A

Mat alpha

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4
Q

Can they undergo sexual

A

Yes but don’t need to, some African populations of cn are mat-a so can sexually reproduce for filament abs basidium formation

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5
Q

Give 3 sources of infection

A

Eucalyptus trees, bird excrement, environmental amoeba (can engulf them)

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6
Q

Where can it access to after dislodging from alveoli in Immunocompromised where spores can proliferate and escape macrophage killing

A

Skin, eyes, bones and cns mainly and trapped in capillaries of body

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7
Q

What’s the diff between mat alpha and a which suggests mat locus is important for infection but don’t know why

A

Alpha is more virulent in mouse models

and preferentially penetrates cns bbb

Also If you look at exp of mat locus when macrophage engulfs, more exp jn mat alpha

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8
Q

Why and where is it a problem (although present everywhere)

A

In sub saharan Africa and south east Asia where there is no access to retroviral drugs for hiv

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9
Q

How many does it kill in sub Africa alone each year

A

1/2 million

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10
Q

Is it the most common cause of fungal meningitis

A

Yes

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11
Q

Can it be transmitted human to human

A

No have to inhale environmental spores

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12
Q

Where is the new gatti strain mixed with local killing healthy (c gatti is not opportunist can cause disease in healthy)

A

Vancouver island since 2002

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13
Q

What is the theory of evolution from amoeba in which suggested they contact cn commonly - suggested reason they have evolved these ‘virulence factors’

A

Acts as a phagocyte with enzymes to degrade it too in a vacuole

So potentially evolved mechanisms for our macrophage escape too
PLUS FEMEMBER THE MAC IN IMMUNOCOMPROMISED MAY NOT BE CAPABLE EG DUE TO LACK OF CD4 mediated activation via ifny

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14
Q

When is mat alpha induced

A

Inside macrophage

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15
Q
  1. Metal related metabolism

Virulence factors

A
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16
Q

Which enzyme requires dinickel and what does it do

A

Urease
Acts to convert urea to ammonia for n source and ph change (alkaline)

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17
Q

Why are bird nests good for ammonia

A

They have a lot of Uric acid

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18
Q

How does nh3 gas ammonia convert to soluble nh4 form which changes ph

A

Acquires proton from environment

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19
Q

Which other pathogen uses urease ph change for advantage

A

H pylori

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20
Q

Where does our high conc body urea come from

A

Liver production

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21
Q

Explain how ph can affect macrophage activation

A

Conversion from T1 type which uses l-arginine to produce NO via nos

Into tissue healing type which produces l-ornithine and urea instead of NO

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22
Q

Osterholzer 2009 study - urease and non protective DC and macrophages in lung
Escape mediated

When infected with ure1 wt mice showed a t2 response. What was this

A

T2 cytokines like il4 and il13 which are immunosuppressive
Pulmonary eosinophils

Arginase conversion of l-arginine

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23
Q

Which enzyme is upreg in t2 response in mice wt and imbalance seen with lower nos2

A

Arginase (l-arginine to l-ornithine/urea)

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24
Q

Ko of ure1 impacted/reduced immature pulmonary dc. What marker was thsi

A

Low cd80/b7

25
Q

How do ph from urease also affect the cns potentially

A

Normally they are trapped in the capillary bed but gain access to cross bbb
From mouse urease mutants. They cannot access the brain

Hypothesised it causes tj disruption in capillary wall cells and allows penetration

26
Q
  1. Iron metabolism

What mechanism do we use in inflammation with infection/chronic diseases to starve fungi from iron and explain anemia in eg cancers

A

Hepcidin exp through il6 in liver

Ub and proteasomal deg of fpn and blocks absorption in enterocytes

27
Q

What special fe efflux pump on phagosome starves then even more

A

Nramp1

28
Q

Which 3 things do cn with high affinity (low fe needed) to import iron as an adaptation - need these to survive under iron starvation because they are high affinity

A

Fre1 reductases converting it to fe2

Then fet3 oxidase converting it back and pairs with ftr1 iron transporter

29
Q

Why is cu toxic (2 reasons)

A

High in Irving Williams series- high affinity can displace eg iron

Also a redox metal which can react with h202 from resp and form hydroxyl radicals causing dna damage

30
Q

Give 2 enzyme examples of displacement killing then

A

Fumarases and aconitases in tca cycle
(Both have 4fe-s)

31
Q

What has the macrophage adapted to pump cu into the phafolysosome

A

When phagosome forms, Atp7a which has cu from atox1 chaperone relocates from tgn to the phagolysosome and pumps cu in

32
Q

What 2 cys rich proteins cu has high affinity for do cn have to cope with cu toxicity - cannot displace metals

Shown through mutant experiments important

A

Mt1/2

33
Q

Which tf when bound to cu induced exp of mt1/2

A

Cuf1 (represses ctr1 exp under these conditions too to stop import)

34
Q

Capsule

A
35
Q

What is the capsule made of and when is it induced

A

Glucoronoxylomannan

Induced by low fe, serum and co2 (physiological co2)

36
Q

What happens within macrophage

A

Induced capsule and also is shed for its escape

Interferes with phagocytosis

37
Q

Is gxm common in aids

A

Yes

38
Q

How does gxm link to complement

A

Potent activator of the alternative pathway

It gets opsonised and depletes c3b opsonin in aids patients and isn’t destroyed by macrophages from opsonisation

39
Q

Which complication seen with crypto meningitis is seen due to the viscous polysach capsule

A

High intracranial pressure

Sue to lymphatic drainage disrupted

40
Q

Why is melanin important for 2 reasons

A

Antioxidant
Scavenges free radicals (block macrophage killing)

And also for uv protection

41
Q

It is produced by laccase, what does this use

A

Brain dipholic compounds like dopamine or epinephrine (explains why induced in cns)

42
Q

4- titan cell formation

What are Titan cells (many characteristics)

A

Large cells of 100microm in diameter
Prevents phagocytosis due to size
Resistant to many stresses in lungs
Polyploid (64 copies of genome)
Rapidly produce many daughter cells

The mechanism is not understood

43
Q

Which acute treatment taken for 2 weeks to get rid of cn in csf

A

AmpB

44
Q

What % of hiv srill die with ampB treatment due to meningitis

A

43%

45
Q

What combination therapy given before it gets to brain

A

AmpB, flucytosine together

Or triple therapy with fluconazole too
To clear sufficiently before maintenance phase

46
Q

What maintenance drug used for 8 weeks to fully clear cn

A

Fluconazole (400g) then reduced after 8 weeks to 200g

47
Q

What 2 type of pseudohyphal forms are there

A

Linked yeast cells

Hyphae with constrictions

48
Q

What is it suggested in environment is importance of pseudohyphae

A

Nutrient and amoeba resistance

49
Q

What’s the difference between mating and fruiting

A

‘Mating is formation of dikaryon then basidium (Or monokaryon)

Fruiting is producing monokaryon with same mat locus type eg alpha x alpha (homothallic mating) - endonuclease activation for spore mat locus recombination

50
Q

Which strain of cryptococcus found to selffilament through unisexual fruiting

A

D (very uncommon to do this but can provide a survival advantage)

51
Q

Why does fruiting explain why alpha is more common

A

More alpha x alpha mating

52
Q

What happens at basidium stage

A

Meiosis and 4 products form 4 basidospore chains on top of basidium

53
Q

Give some conditions when hyphal growth/ mating is preferred

A

Below 37c, darkness, N starvation

54
Q

What in mouse models was found 37c is required for

A

Required for systemic infection (yeast is more virulent than filamented)

55
Q

What did pseudohyphal injection into mouse cns do

A

Failed to kill them and eventually the fungi depleted showing yeast from is more virulent

56
Q

Why is prophylactic fluconazole given

A

High csf penetration

57
Q

What is intracranial pressure increase associated with in meningitis

A

Visual/hearing loss and strong headaches

58
Q

What wbc count in csf extremely low in hiv allows persistence

A

20 cells/microlitre

59
Q

Is there evidence yeast can stay dormant eg in lung granulomas and infect years later?

A

Yes

Microbiota On Mucosal (22 decks)

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