Die Rolle des TEA/ATTS-Transkriptionsfaktors CaTEC1p bei der Hyphenbildung und Virulenz von Candida albicans

The ability of the human pathogenic fungus Candida (C.) albicans to change his cell morphology between a yeast and a Hypheform (dimorphism) is regarded as an important virulence property. In the course of such morphological development processes is the spatial and temporal expression of the phase-specific genes in fungi such as controlled in higher eukaryotes of transcription factors. In C. albicans, a new member of the family of the TEA / ATTS transcription factors have been identified [1, 2]. According to its functional homology to the Saccharomyces (S.) cerevisiae TEC1 this gene C. albicans TEC1 (CaTEC1) was called. CaTEC1 is predominantly in the hyphal phase of C. albicans expressed. Also has a homozygous catec1/catec1-Mutante in vitro defects in hyphae formation. These data already indicate that CaTEC1 fulfills an important regulatory role in the development of C. albicans hyphae. As part of the thesis presented here is also shown that C. albicans has deficiencies in the absence of CaTEC1 virulence. In catec1/catec1-Mutante be important virulence factors, such as the hyphen specific proteinase SAP4, SAP5 SAP6 and no longer expressed and Evasion from macrophages is suppressed in vitro. In a murine model of systemic candidiasis is catec1/catec1-Mutante the virulence of attenuated, although formed in vivo in the infected organs and on the vaginal epithelium, hyphen similar cell lines. Furthermore, it was shown that the morphogenetic defects and virulence deficiencies of C. albicans strains with mutations in the signaling cascades of hyphae formation which comprise Ras1p, a MAPK cascade and a cAMP-signaling pathway are compensated by the controlled overexpression of CaTEC1 . Moreover, the virulence of a C. albicans wild type strain is amplified by the CaTEC1 overexpression. From these results it could be concluded that the different signal transduction pathways converge on the transcription factor CaTec1p to ensure the activation of selected virulence gene, which are essential for the pathogenicity of C. albicans. The TEA / ATTS transcription factors have been attributed only regulatory functions in development processes. In this work, a member of this family was identified with the C. albicans transcription factor CaTec1p for the first time, the regulator a central role in virulence in microbial pathogenicity takes over.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Friedrich-Alexander-Universität Erlangen-Nürnberg

Year dc:date.issued

2003

Author dc:creator

• Schweizer, Anja

Language dc:language

en