lec 14-15 fungal pathogens Flashcards
fungi
eukaryotes
absorb nutrients by breaking down organic material into simple molecules - saprophytes
can be sexual or asexual - spore formation
fungi structure
Each organism (thallus) is unicellular to filamentous,
possess branched somatic structures (hyphae)
cell walls contain glucan or chitin or both, and containing true nuclei
types of fungi
moulds
filamentous
dimorphic
superficial mycoses
outermost layers of skin, hair nails and mucous membranes
e.g. dermatophytes and candida
mycosis
fungal infection of animals
caused by inhalation of fungal spores or localised colonisation of the skin
dermatophytes
superficial mycoses
filamentous fungi commonly found in soil
colonise outer keratin tissues, causing inflammation
cause athletes foot, ring worm
e.g. microsporum
3 groups of dermatophytes
anthrophilic - found in man
zoophilic - resevoir is animals - if enter humans, causes severe inflammatory infections
geophilic - found in soil, exist as microbes
candida
superficial mycoses
opportunistic fungus causes thrush commensal organism - can be pathogenic to immunocompromised individuals present in mouth and GI tract e.g. candida albicans
subcutaneous mycoses
fungi enter through piercing/puncture wound
involves dermis, subcutaneous tissues, muscle and fascia
causes chronic infections
e..g chromoblastomycis
chromoblastomycis
subcutaneous mycoses
causes chronic fungal infection
fungi become implanted under skin e.g. thorn, splinter
primary pathogens
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
thermally dimorphic
can reproduce in two different states
mycelial saprotrophic form grows at 25 degrees
parasitic yeast-like form grows at 37 degrees
opportunistic pathogens
have the potential to be infectious
cause deep mycosis
only infect those who are immunocompromised or damaged lungs
how do primary pathogens invade host/route of infection
inhalation of spores
how do opportunistic pathogens invade host/route of infection
via respiratory or alimentary tract
aspergillosis
fungal infection causes by Aspergillus sp.
spores present in normal air but just dont normally cause disease to healthy individuals
deep seated/systemic infection
fungal infection of internal organs
may disseminate to multiple organs
top 4 fungal killers
- Cryptococcus
- Candida
- Aspergillus
- Pneumocystis
all opportunistic
candida auris
an emerging pathogen
causes superficial and systemic diseases
pseudogymnoascus destructans
emerging animal fungal disease
causes white nose syndrome in bats
high potential it could lead to extinctions
Batrachochytrium dendrobatidis
emerging animal fungal disease
skin infecting amphibian fungus
hypervirulent
globally dispersed
causing amphibian decline
virulence
ability to cause disease
continuous variable
impacted by host response
identification of virulence factors
reverse and forward genetics
reverse genetics to identify virulence factors
candidate gene approach
associations between genetic variation in specific genes of interest and in phenotypes
forward genetics to identify virulence factors
genome wide approach
scan the entire genome for common genetic variation
koch’s molecular postulates
4 criteria establishing a causative relationship between a microbe and disease
guides the identification of microbial genes encoding virulence factors
method of confirmation of virulence factors
disrupt target gene to create mutant strain
demonstrate attenuated virulence of mutant
reintroduction of gene restores virulence
characteristics of candida albicans
cause of candidosis largely asexual diploid - 8 chromsomes polymorphic fungus CUG codon reassigned
4 main morphologies of candida albicans
yeast cell
hyphae
pseudohyphae
chlamydospore
what type of signal triggers morphogenesis
environment signals
tissue penetration
hyphal growth
vascular dissemination
yeast growth
what promotes hyphal growth
temperature >35 neutral pH High PCO2 Low PO2 N- or C- terminal starvation low cell densities - quorum sensing
what promotes yeast cell growth
temperature <35
acidic pH
NH4+ ions
High cell densities - quorum sensing
4 stages of candida albicans infection
- adhesion and colonisation to host surfaces
- penetration of epithelia and nutrient procurement
- vascular dissemination
- endothelial colonisation and penetration
what surfaces do candida albicans adhere to
epithelial surfaces
endothelial surfaces
medical devices
self-association - biofilms
important adhesion factors for C. Albicans
Mannoproteins
- enriched on outer cell surface
- encoded by gene families
ALS3
- Agglutin-like sequence
- cell wall proteins
- bind to cadherins
mechanisms of c. albicans invasion and penetration
- induced by endocytosis
- fungal ‘invasin’ interacts with host cell surface proteins
- triggers fungal engulfment (endocytosis) - induced by active penetration
- directly into host cells or between junctions
c. albicans biofilm features
form on biotic and abiotic surfaces
structured assemblies in ECM
display inherent resistance to antifungals and host defences
c. albicans biofilm formation
impacted by quorum sensing and polymicrobial interactions
4 steps:
- attachment
- initiation
- maturation
- dispersal
biofilm
- attachment
adherence of yeast cells to substrate
biofilm
- initiation
formation of micro-colony
biofilm
- maturation
hyphal development and ECM production
mature biofilm is a mix of molecules
favours anaerobic conditions - alcohol production
biofilm
- dispersal
alcohol production inhibits filamentation
release of non-adherent yeast cells
Candida can escape the alcohol poisoned environment
host defences to candida
flushing mechanisms
molecular recognition
phagocytosis
immune response
hyphae direct virulence
invasion and tissue damage
thigmotropism
escape from phagocytes
indirect virulence of hyphae
through genes co-regulated with morphogenesis
why is candida albicans adhesion necessary
to colonise mucosal surfaces
role of secreted hydrolytic enzymes in virulence
nutrient acquisition
combat host defences
adhesion
stress associated with immune response
phagocytosis
respiratory burst
cytokine burst
phagocytosis as a result of immune response
change in pH
low amino acid availability
lack of glucose/iron
respiratory burst as a result of immune response
reactive oxygen species
reactive nitrogen species
cytokine burst as a result of immune response
inflammatory response
elevated temperature
factors virulence is reliant on
adhesion invasion penetration morphogenesis biofilm secreted hydrolases stress response immunomodulation
