Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Poster number: 22
Candida albicans unique genes: specific roles in host cell
damage
Duncan Wilson 1 , Francois Mayer 1 , Ilse Jacobsen 1 , Bernhard Hube 1,2
1 Hans Knoell Institute, Jena, Germany; 2 Friedrich Schiller University, Jena, Germany
Candida albicans is amongst the most pathogenic species of fungi and causes both
superficial (high prevalence) and systemic (high mortality) infections. Because the
major human pathogenic fungal species are distantly related, we hypothesized that
they may possess unique genes which account for their high pathogenic potential.
Using C. albicans as a model pathogen, we performed in silico genome subtraction
and transcriptional analysis to identify [C. albicans] species-unique genes
expressed during infection. Gene deletion combined with a series of infection
models (including biochemical analysis of cellular damage and fluorescence
microscopy-based morphological, adhesion and invasion assays for in vitro
epithelial, endothelial and macrophage infection models, as well as an in vivo mouse
virulence model) were used to determine the role of C. albicans unique genes during
infection.
A total of 65 C. albicans unique genes, expressed during infection, were identified
and six were deleted. Five of the resultant homozygous mutants exhibited
significantly altered phenotypes in at least one infection model. One gene, PGA16,
was found to be required both for epithelial destruction and virulence in a mouse
model of hematogenously disseminated candidiasis. Furthermore, this gene was
required for hyphal ramification and optimal dissemination within epithelia.
This study therefore provides molecular evidence that filament branching of a fungal
pathogen contributes to virulence.
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