Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
Candida Infection Biology – fungal armoury, battlefields ... - FINSysB
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Poster number: 40<br />
Wall proteins, absolute quantification and concatenated<br />
vaccines: A new approach for <strong>Candida</strong> albicans therapy?<br />
Clemens J. Heilmann, Alice G. Sorgo, Henk L. Dekker, Stanley Brul, Chris<br />
G. de Koster, Leo J. de Koning and Frans M. Klis<br />
Swammerdam Institute for Life Sciences, Universiteit van Amsterdam, Science Park 904,<br />
1098XH Amsterdam<br />
The cell wall and especially the proteins that are covalently anchored to it are the<br />
first site of host-pathogen interaction. The wall proteins are promising targets for<br />
the development of diagnostic biomarkers and vaccines. Previously, we described<br />
the relative quantitative changes in up to 21 wall proteins during the yeast-to-hypha<br />
transition (1) and upon exposure of cells to fluconazole (2). We identified hyphaassociated<br />
wall proteins (Als3, Hwp2, Hyr1, Plb5, Sod5) conferring increased<br />
adhesion and resistance to host defenses and yeast-associated proteins (Rhd3,<br />
Sod4, Ywp1), which probably play a role in host dispersal and immune evasion.<br />
Morphotype-independent proteins (Cht2, Crh11, Ecm33, Mp65) are mainly involved<br />
in wall structure and remodeling.<br />
However, relative quantification can only provide indications of how protein<br />
abundance changes in response to an environmental change. To compare the<br />
abundances of different proteins, absolute quantification is required. We are<br />
developing a strategy for absolute quantification based on 15 N metabolic labeling<br />
and concatenated proteins (Q-CON-CAT). By using the same 15 N reference culture<br />
that was also used for relative quantification and determining the absolute amount<br />
of a particular protein, we will be able to recalculate the relative quantification results<br />
into absolute values.<br />
These absolute values will be informative for the construction of peptide-based<br />
vaccines. We propose that by concatenating peptides that are predicted to be<br />
highly immunogenic and originate from abundant wall proteins an effective Q-CON-<br />
CAT vaccine protein can be generated.<br />
(1) Hyphal Induction in the human <strong>fungal</strong> pathogen <strong>Candida</strong> albicans reveals a characteristic wall protein<br />
profile. Heilmann CJ, Sorgo AG, Siliakus AR, Dekker HL, Brul S, de Koster CG, de Koning LJ, Klis FM.<br />
Microbiology. 2011 May 20.<br />
(2) The effects of fluconazole on the secretome, the wall proteome and wall integrity of the clinical fungus<br />
<strong>Candida</strong> albicans. Sorgo AG, Heilmann CJ, Dekker HL, Bekker M, Brul S, de Koster CG, de Koning LJ,<br />
Klis FM.Eukaryot Cell. 2011 May 27.<br />
We are grateful to the European Commission for funding the <strong>FINSysB</strong> Marie Curie Initial Training Network<br />
(PITN-GA-2008-214004).<br />
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