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

Poster number: 12
Functional analysis of C. albicans infection-associated
genes with unknown function during interaction with host
cells and in complex infection models
Ilse D. Jacobsen 1 , Duncan Wilson 1 , Francois Mayer 1 , Bernhard Hube 1,2
1 Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product
Research and Infection Biology - Hans-Knöll-Institute, Jena, Germany; 2 Friedrich-Schiller
University, Jena
Candida albicans is able to cause a variety of clinical infections. We hypothesized
that C. albicans unknown function genes, which were transcriptionally upregulated
during oral infections, liver invasion or incubation in human blood (“infection
associated genes”) might contribute to the infection process. We selected a subset
of infection-associated genes with unknown function for further analysis.
Twentyfour isogenic deletion mutants were constructed and subsequently analyzed
both in vitro and in infection models of increasing complexity. Sixteen mutants were
impaired in their ability to damage monolayers of human endothelial and/or
epithelial cells. Within this subset, seven mutants additionally displayed decreased
stress resistance in vitro. Only two mutants showed filamentation defects. To
determine whether the deleted genes influenced virulence in more complex
infections models, all 24 mutants were tested in ovo for their ability to kill chicken
embryos infected on the chorio-allantoic membrane. We recently showed that
mortality in this model depends on the fungal ability to invade the membrane and
that the pro-inflammatory host response likely contributes to pathogenesis.
Surprisingly, only seven mutants were attenuated in this model, of which five were
also attenuated in damaging epithelial cells in vitro. Three of the mutants, which
were attenuated in ovo, and one mutant, which was attenuated in damaging
endothelial and epithelial cells but fully virulent in chicken embryos, were
subsequently analyzed in a systemic mouse model. Virulence in mice mirrored the
results obtained in ovo.
Our results demonstrate that genes essential for causing full damage of epithelial
or endothelial cells in vitro are not necessarily crucial for full virulence in complex
infection models. We conclude that either such damage potential is not critical for
full virulence in the complex host situation or that the greater complexity of the
environment in animal models stimulates additional fungal regulatory networks
leading to compensation of the defect.
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