Candida Albicans Flashcards
What types of patients suffer superficial infections of C. albicans?
What types of patients suffer systemic infections of C. albicans?
AIDs patients suffer superficial infections while Cancer patients and transplant patients following immunosuppression suffer from systemic infections.
What allows C. albicans to become a virulent pathogen from a commensal organism?
A myriad of virulence factors that are expressed under certain predispositions from the host. These virulence factors are: phenotypic switching, dimorphism, adhesion factors and extracellular lipolytic and proteolytic enzymes.
What initiates change from a yeast form to a hyphal form?
The formation of hyphae is inhibited by what?
An increased nutrient supply and an increase in temperature (37 degrees).
Farnesol which is a quorum sensing molecule.
Describe how HGC1 controls dimorphism.
HGC1 is a G1-Cyclin-related protein which is not expressed in yeast cells but is expressed in Hyphae. It’s different from other G1 cyclins as the expression of it does not change over the life cycle of the hyphae. Deletion mutants of this gene resulted in no hyphae growth which impaired virulence drastically.
How is adherence achieved?
It is achieved through the use if phospholipases and proteases which break down the host cell membrane. Electrostatic charges and van der waals forces also allow it to adhere. This allows C. albicans to adhere to a wide range of tissue types.
Describe Biofilm formations and how they are causing greater nosocomial infections.
Approximately one half of nosocomial C. albicans infections are caused through biofilm formation of implanted medical devices, such as catheters, heart valves and pacemakers. These devices allows the fungus to bypass the skin anatomical barrier and be placed straight into tissues. Growth is different as well as gene expression patterns with the Biofilms being more resistant to anti-fungal agents.
A mutation in what genes causes C. albicans to be unable to form a biofilm.
Eap1-1/eap1-2
What are the two types of C. albicans yeast cell?
Describe their morphology and their virulence.
What controls their ability to switch phenotypes?
White and opaque cells.
White cells have a classic rounded shape while opaque cells have a more elongated shape. These types of cells can be more or less virulent depending on where they are. Their switch to opaque cells is needed for sexual mating.
The MTL locus controls their switching.
What does the MTL locus control and code for?
Controls phenotypic switching,
The locus contains the WOR1 gene which codes for the Wor1p transcription factor. This induces the opaque state in MTL homozygotes and a pseudo opaque state in heterozygotes.
What types or hydrolytic enzymes are used by C. albicans as virulence factors?
Proteases,
Phospholipases,
Lipases,
Esterases.
What functions do proteases aid in during C. albicans infection?
What are the four categories of proteases?
Breaking down host proteins for a nutrient supply, to aid tissue invasion or to aid adherence. They are also needed to damage host proteins needed in their immune defence system.
Serine proteases, metallo proteases, cysteine proteases and aspartyl proteases.
What category of proteases do C. albicans proteases belong to? What are they collective known as and what are they essential for? What virulence factors do this family of proteases aid in?
They all belong to the aspartyl proteases family, and are collectively known as SAPs. SAPs are essential for growth when protein is the sole nitrogen source.
They aid adhesion, phenotypic switching and dimorphism (hyphal formation).
How many SAPs are there in C. albicans?
What is there molecular size?
What is their pH optima?
What are SAPs inhibited by?
There are 10 SAPs in C. albicans. They are encoded by SAPs 1-10. They have a size between 35-50kDa. Generally aspartyl proteases possess low pH optima making them known as acid proteases, however SAPs have different pH optima meaning that they can colonise different areas of the host with different pHs.
They are inhibited by pepstatin A which is produced by Streptomycces
How are SAPs generated?
What are the pH optimas for some of the SAPs?
SAPs are synthesised as precursors which are transported via secretory pathways (at this point they are 60aas longer than the mature protein). SAPs 1-3 have a pH optima of 3-5. SAPs 4-6 have a pH optima of 5-7.
SAPs possess distinctive promoter regions which means they can be switched on or off by different regulators in response to different conditions.
SAPs 1-8 are secreted where whereas SAPs 9-10 are what?
1-8 are secreted into the extracellular space whereas 9-10 are membrane bound.
