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Characterization of genes encoding for cell surface proteins induced during hostpathogen interaction

 
: Zavrel, M.; Hernandez, R.; Sohn, K.; Hauser, N.; Rupp, S.

Federation of European Biochemical Societies -FEBS-, Copenhagen; Federation of European Microbiological Societies -FEMS-:
3rd FEBS advanced lecture course Human Fungal Pathogens (HFP). Molecular mechanisms of host-pathogen interactions and virulence. Abstract book : May 2-8, 2009 La Colle sur Loup, France
La Colle sur Loup, 2009
pp.179
FEBS advanced lecture course Human Fungal Pathogens (HFP) <3, 2009, La Colle sur Loup>
English
Abstract
Fraunhofer IGB ()

Abstract
Candida albicans is a commensal organism living on skin and mucosal surfaces of humans. Its
presence becomes a problem in immunocompromised patients where it may turn into an
opportunistic pathogen. Candida colonizes various host niches including skin, gastrointestinal
and the urogenital tract, which offer various environments in terms of pH and nutrient
availability. The cell surface of the fungus is the site of direct interaction of Candida with the
host, mediating the environmental sensing, adhesion and also interaction with the host immune
system. Since the cell wall is not present in humans its components are a prime target for drug
development. To reveal whether C. albicans is able to specifically react to different epithelial
tissue or other surfaces in a specific manner we used transcriptional profiling in order to
identify genes differentially regulated during adhesion focusing on cell surface proteins. One
of the genes identified was termed Adhesion Upregulated Factor – AUF8. The respective
protein is predicted to be localized in the plasma membrane carrying four transmembrane
domains. AUF8 is upregulated in an adhesion dependent manner with the strongest induction
on intestinal tissue model after two hours of interaction. For AUF8 we identified six
homologues in the C. albicans genome, of which five together with AUF8 are in one 10 kb
gene-cluster. When heterologously expressed in S. cerevisiae Auf8p is localized to the plasma
membrane. Deletion studies indicate that the AUF genes may be required for fitness during
stationary phase. However, its function during adhesion is still unclear. Other proteins encoded
by genes upregulated during adhesion and first steps of invasion are localized in the cell wall.
The functional studies of PGA7, PGA23 and PRA1 with regards to adhesion and invasion as
well as cell wall stability were performed using deletion and overexpression strains. Our
studies qualify PGA7 and PGA23 as structural elements of the cell wall rather than adhesins.

: http://publica.fraunhofer.de/documents/N-154077.html