lec 14-15 fungal pathogens

Question 1

fungi

Answer 1

eukaryotes
absorb nutrients by breaking down organic material into simple molecules - saprophytes

can be sexual or asexual - spore formation

Question 2

fungi structure

Answer 2

Each organism (thallus) is unicellular to filamentous,

possess branched somatic structures (hyphae)

cell walls contain glucan or chitin or both, and containing true nuclei

Question 3

types of fungi

Answer 3

moulds
filamentous
dimorphic

Question 4

superficial mycoses

Answer 4

outermost layers of skin, hair nails and mucous membranes

e.g. dermatophytes and candida

Question 5

mycosis

Answer 5

fungal infection of animals

caused by inhalation of fungal spores or localised colonisation of the skin

Question 6

dermatophytes

Answer 6

superficial mycoses

filamentous fungi commonly found in soil
colonise outer keratin tissues, causing inflammation
cause athletes foot, ring worm
e.g. microsporum

Question 7

3 groups of dermatophytes

Answer 7

anthrophilic - found in man
zoophilic - resevoir is animals - if enter humans, causes severe inflammatory infections
geophilic - found in soil, exist as microbes

Question 8

candida

Answer 8

superficial mycoses

opportunistic fungus 
causes thrush 
commensal organism - can be pathogenic to immunocompromised individuals
present in mouth and GI tract
e.g. candida albicans

Question 9

subcutaneous mycoses

Answer 9

fungi enter through piercing/puncture wound
involves dermis, subcutaneous tissues, muscle and fascia
causes chronic infections
e..g chromoblastomycis

Question 10

chromoblastomycis

Answer 10

subcutaneous mycoses

causes chronic fungal infection
fungi become implanted under skin e.g. thorn, splinter

Question 11

primary pathogens

Answer 11

cause disease as a result of their presence

all thermally dimorphic
common in endemic regions
filamentous and spore forming

infect healthy individuals

e.g. blastomyces dermatidis

Question 12

thermally dimorphic

Answer 12

can reproduce in two different states

mycelial saprotrophic form grows at 25 degrees
parasitic yeast-like form grows at 37 degrees

Question 13

opportunistic pathogens

Answer 13

have the potential to be infectious

cause deep mycosis

only infect those who are immunocompromised or damaged lungs

Question 14

how do primary pathogens invade host/route of infection

Answer 14

inhalation of spores

Question 15

how do opportunistic pathogens invade host/route of infection

Answer 15

via respiratory or alimentary tract

Question 16

aspergillosis

Answer 16

fungal infection causes by Aspergillus sp.

spores present in normal air but just dont normally cause disease to healthy individuals

Question 17

deep seated/systemic infection

Answer 17

fungal infection of internal organs

may disseminate to multiple organs

Question 18

top 4 fungal killers

Answer 18

• Cryptococcus
• Candida
• Aspergillus
• Pneumocystis

all opportunistic

Question 19

candida auris

Answer 19

an emerging pathogen

causes superficial and systemic diseases

Question 20

pseudogymnoascus destructans

Answer 20

emerging animal fungal disease

causes white nose syndrome in bats
high potential it could lead to extinctions

Question 21

Batrachochytrium dendrobatidis

Answer 21

emerging animal fungal disease

skin infecting amphibian fungus
hypervirulent
globally dispersed
causing amphibian decline

Question 22

virulence

Answer 22

ability to cause disease
continuous variable
impacted by host response

Question 23

identification of virulence factors

Answer 23

reverse and forward genetics

Question 24

reverse genetics to identify virulence factors

Answer 24

candidate gene approach

associations between genetic variation in specific genes of interest and in phenotypes

Question 25

forward genetics to identify virulence factors

Answer 25

genome wide approach scan the entire genome for common genetic variation

Question 26

koch's molecular postulates

Answer 26

4 criteria establishing a causative relationship between a microbe and disease guides the identification of microbial genes encoding virulence factors

Question 27

method of confirmation of virulence factors

Answer 27

disrupt target gene to create mutant strain demonstrate attenuated virulence of mutant reintroduction of gene restores virulence

Question 28

characteristics of candida albicans

Answer 28

``` cause of candidosis largely asexual diploid - 8 chromsomes polymorphic fungus CUG codon reassigned ```

Question 29

4 main morphologies of candida albicans

Answer 29

yeast cell hyphae pseudohyphae chlamydospore

Question 30

what type of signal triggers morphogenesis

Answer 30

environment signals

Question 31

tissue penetration

Answer 31

hyphal growth

Question 32

vascular dissemination

Answer 32

yeast growth

Question 33

what promotes hyphal growth

Answer 33

``` temperature >35 neutral pH High PCO2 Low PO2 N- or C- terminal starvation low cell densities - quorum sensing ```

Question 34

what promotes yeast cell growth

Answer 34

temperature <35 acidic pH NH4+ ions High cell densities - quorum sensing

Question 35

4 stages of candida albicans infection

Answer 35

1. adhesion and colonisation to host surfaces 2. penetration of epithelia and nutrient procurement 3. vascular dissemination 4. endothelial colonisation and penetration

Question 36

what surfaces do candida albicans adhere to

Answer 36

epithelial surfaces endothelial surfaces medical devices self-association - biofilms

Question 37

important adhesion factors for C. Albicans

Answer 37

Mannoproteins - enriched on outer cell surface - encoded by gene families ALS3 - Agglutin-like sequence - cell wall proteins - bind to cadherins

Question 38

mechanisms of c. albicans invasion and penetration

Answer 38

1. induced by endocytosis - fungal 'invasin' interacts with host cell surface proteins - triggers fungal engulfment (endocytosis) 2. induced by active penetration - directly into host cells or between junctions

Question 39

c. albicans biofilm features

Answer 39

form on biotic and abiotic surfaces structured assemblies in ECM display inherent resistance to antifungals and host defences

Question 40

c. albicans biofilm formation

Answer 40

impacted by quorum sensing and polymicrobial interactions 4 steps: 1. attachment 2. initiation 3. maturation 4. dispersal

Question 41

biofilm 1. attachment

Answer 41

adherence of yeast cells to substrate

Question 42

biofilm 2. initiation

Answer 42

formation of micro-colony

Question 43

biofilm 3. maturation

Answer 43

hyphal development and ECM production mature biofilm is a mix of molecules favours anaerobic conditions - alcohol production

Question 44

biofilm 4. dispersal

Answer 44

alcohol production inhibits filamentation release of non-adherent yeast cells Candida can escape the alcohol poisoned environment

Question 45

host defences to candida

Answer 45

flushing mechanisms molecular recognition phagocytosis immune response

Question 46

hyphae direct virulence

Answer 46

invasion and tissue damage thigmotropism escape from phagocytes

Question 47

indirect virulence of hyphae

Answer 47

through genes co-regulated with morphogenesis

Question 48

why is candida albicans adhesion necessary

Answer 48

to colonise mucosal surfaces

Question 49

role of secreted hydrolytic enzymes in virulence

Answer 49

nutrient acquisition combat host defences adhesion

Question 50

stress associated with immune response

Answer 50

phagocytosis respiratory burst cytokine burst

Question 51

phagocytosis as a result of immune response

Answer 51

change in pH low amino acid availability lack of glucose/iron

Question 52

respiratory burst as a result of immune response

Answer 52

reactive oxygen species | reactive nitrogen species

Question 53

cytokine burst as a result of immune response

Answer 53

inflammatory response | elevated temperature

Question 54

factors virulence is reliant on

Answer 54

``` adhesion invasion penetration morphogenesis biofilm secreted hydrolases stress response immunomodulation ```