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

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