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

Deciphering the role of CUG mistranslation on Candida
albicans adhesion and cell surface variation
Isabel Miranda 1,2 , Ana Silva-Dias 1,2 , Rita Rocha 1 , Teresa Gonçalves 3 , Cidália
Pina-Vaz 1,2,4 , Scott G. Filller 5,6 and Acácio G. Rodrigues 1,2,7
1 Department of Microbiology, Faculty of Medicine, University of Porto, 2 Cardiovascular
Research & Development Unit, Faculty of Medicine, University of Porto, Portugal, 3 Center
for Neurosciences and Cell Biology, Institute of Microbiology, Faculty of Medicine, University
of Coimbra, Portugal; 4 Department of Microbiology, Hospital S. João; 5 Department.of
Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center,
Torrance, California, USA; 6 David Geffen School of Medicine at UCLA, Los Angeles,
California, USA; 7 Burn Unit and Department of Plastic and Reconstructive Surgery, Hospital
S. João, Portugal.
Interactions with the surrounding environment represent a continuous stressing
challenge for microorganisms. Until now, the mechanisms regulating changes in
cell-surface in the most common human fungal pathogen still remain unclear. In
Candida albicans, the CUG codon is naturally mistranslated as two biochemically
distinct residues, serine and leucine. Interestingly, genes encoding adhesins such
as the ALS family are particularly enriched in CUG codons. In order to evaluate the
role of CUG mistranslation in C. albicans adhesion, we compared the behavior of
two strains: a wild-type, in which 3% of CUG codons are mistranslated as leucine
and a highly CUG mistranslating strain wherein 28% of CUG codons are
mistranslated as leucine. We found that the increase in leucine misincorporation
enhances cell wall hydrophobicity and the capacity of yeast cells to adhere to
biomaterials. This adhesion phenotype was further confirmed in Saccharomyces
cerevisiae, through expression of C. albicans ALS3 gene in its two isoforms: Als3p-
Leu and Als3p-Ser. Als3p-Leu yeasts prompted a strong adhesion phenotype,
resulting in flocculation in liquid media and two-to-fivefold more adhesion than
Als3p-Ser. The cell wall variability generated by CUG mistranslation may not be
confined to adhesion and could be relevant for immune system evasion. Indeed,
highly CUG mistranslating cells were less susceptible to phagocytosis by murine
macrophages than wild-type, probably due to the more efficient glucan masking
caused by CUG mistranslation. We propose that CUG mistranslation was
maintained during C. albicans evolution due to its potential to generate cell surface
variability.
A Silva-Dias is supported by a FCT (Fundação Ciência e Tecnologia) doctoral grant
SFRH/BD/44896/2008; I Miranda is supported by Ciência 2008 (FCT) and European Social Fund.
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