Candida albicans Flashcards
Virulence
- Ability to cause disease
- Continuous variable defining strains within a species
fully virulent= the average strain
hypervirulent= more virulent then average
highly attenuated= less virulent - Significantly impacted by host defences
Disease from microbial attack
- Damage results from a range of host pathogen interactions
There can be damage due to:
- Microbial factors
- Host immune overreaction
Most symptoms are from the host immune response
Identification and confirmation of virulence factors
Identification
- Reverse genetics: candidate gene approach
- Forward genetics: genome wide approach
Confirmation, molecular Koch’s postulates
- disrupt target gene to create mutant strain
- demonstrate attenuated virulence of mutant
- reintroduction of gene restores virulence
Koch’s postulates
To test whether a microbe is responsible for making an animal sick
1. The microbe must always be present in the organism showing symptoms
2. It must be removed from the organism and grown outside its host
3. The isolated microbe is used to infect a healthy host
This newly infected organism must show the same symptoms as the original host
4. Isolate the same microbe from the newly infected host
Virulence of Candida albicans
- Virulence is multi-factorial
- Host recognition biomolecules, adhesins
- Morphogenesis
The reversible transition between unicellular yeast and filamentous - Secreted aspartyl proteases and phospholipases
- Phenotypic switching is accompanied by changes in antigen expression, colony morphology + tissue affinities
- Obtaining nutrients
- Oppose host defence (constant flushing mechanisms in epithelia, molecular recognition + immune response)
Stages of Candida albicans infection
- Adhesion and colonisation of epithelial tissue
(important as a commensal, causing superficial disease and the first stage of systemic disease) - Epithelial penetration
- Vascular dissemination
Penetrates into the blood stream and spreads - Endothelial colonisation and penetration
Characteristics of Candida albicans
- Diploid organism
- Largely asexual
- Polymorphic fungus
- CUG codons reassigned
- Primary cause of candidosis
Candida albicans
The environmental signals triggering hyphal morphogenesis
- It is polymorphic: yeast, pseudohyphae, opaque, hyphae + chlamydospore
- hyphal growth is promoted by:
temperature >35, serum, neutral pH, high pCO2, low pO2, N- or C- starvation and matrix embedded growth - yeast growth is promoted by:
acidic pH, temperature < 35, NH4+ ions
Role of hyphal morphology in virulence
- Hyphae= tissue penetration
- Yeast= vascular dissemination
If there are mutants that are blocked and can only form either hyphae or yeast, they are attenuated - Hyphae play both direct and indirect roles in virulence
Direct roles: Invasion and tissue damage, thigmotropism + escape from phagocytes
Indirect roles: through genes co-regulated with morphogenesis - The transition to filamentous growht is important for biofilm formation and for invasive growth in vivo. Induction of the hyphal form also correlates with increased expression of virulence factors, including adhesin proteins that promote biofilm formation, secreted lytic enzymes that facilitate invasive growth and inactivate the host complement pathway + antioxidant enzymes that counteract the immune system
Candida albicans and phagocytes
- The candida albicans, yeast are taken up by phagocytes
- When candida is phagocytosed, it switches to hyphal growth and it bursts out of the phagocyte
Candida albicans adhesion
- Adhere to epithelia for superficial infection
- It adheres to endothelial tissue and medical devices
- It forms a biolfilm in a catheter
- Candida can grow with other bacteria in a biofilm such as Streptomyces
Key adhesins: - cell surface mannoproteins Enriched on cell surface - cell wall proteins ALS family 8 members Als3 is important in adhesion
Candida albicans invasion and penetration
- It interacts with a variety of host cells during the disease process
- It needs to invade through epithelia and endothelial surfaces
2 routes to invade cells
- Induced endocytosis
- Active penetration
Candida route to invade cells
Induced endocytosis
- Candida adheres to host tissue
- It expresses other proteins on its cell surface called invasins
The invasins interact with host receptors and result in that cell, even though it is usually non phagocytic, taking up the candida through endocytosis
Active penetration
- Directly into host cells or between junctions
- When moving directly into host cells: hyphae adhere to host tissue and you get apical growth from the tip and it uses force to move down through
- Between tissue, candida secretes hydrolytic enzymes (proteases) to breakdown proteins between cells and it can use its thigmotropism to find its way through
Candida and biofilms
- It forms on a variety of biotic and abiotic surfaces
- Structured assemblies encased in extracellular matrix
- Display inherent resistance to antifungals and host defences
- Quorum sensing and polymicrobial interactions impact on formation
Stages of biofilm formation
Attachment - Adherence of yeast cells to substrate
Initiation- Formation of microcolony
Maturation- Hyphal development + ECM production
Dispersal- Release of non adherent yeast cells
