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

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Revisiting the Hog Pathway of C. glabrata<br />

136<br />

Poster number: 13<br />

Zeljkica Jandric, Wolfgang Reiter, Gustav Ammerer, Christoph Schüller<br />

Max F. Perutz Laboratories, Department of Biochemistry University of Vienna, Dr.Bohr-<br />

Gasse 9/5, A-1030 Vienna, Austria<br />

Signal transduction networks mediated by mitogen – activated protein kinases<br />

(MAPK) play essential roles in eukaryotic cells. Yeast cells have developed<br />

osmoadaptation pathways to cope with osmotic changes in the microenvironment.<br />

In Saccharomyces cerevisiae five MAPK pathways are well characterized. One of<br />

these, especially associated with stress response, is the High Osmolarity Glycerol<br />

(HOG) pathway . Stress induced phosphorylation triggers the activation of the key<br />

MAPK, Hog1. After being phosphorylated by the upstream MAPKK Pbs2, Hog1<br />

enters the cell nucleus and modulates the transcription of its target genes.<br />

Orthologues of the all HOG pathway compounds found in Saccharomyces<br />

cerevisiae have been identified in fungi and animals.<br />

The human <strong>fungal</strong> pathogen <strong>Candida</strong> glabrata is closely related to Saccharomyces<br />

cerevisiae. It is a common commensal but in immunocompromised cancer and<br />

transplant patients or elder persons it can turn into an opportunistic pathogen.<br />

Depending on the host environment, <strong>Candida</strong> glabrata has to adapt to<br />

environmental changes during invasion and adaptation steps. We investigated the<br />

role of Hog1 in <strong>Candida</strong> glabrata. Several stress sources were used to identify HOGspecific<br />

phenotypes and to analyze the role of Hog1 in <strong>Candida</strong> glabrata. As<br />

expected, the deletion of Hog1 caused osmostress hypersensitivity. Physiological<br />

stress conditions, such as nutrients starvation, were simulated by infection of<br />

macrophages with <strong>Candida</strong> glabrata and determination of the number of surviving<br />

<strong>Candida</strong> cells. Cghog1∆ cells showed a much higher sensitivity to macrophages<br />

compared to wild type cells. Further investigations focus on stress induced gene<br />

transcription in Cghog1∆ cells and comparison of the transcription pattern to cells<br />

without Hog1 deletion.

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