A conserved fungal hub protein involved in adhesion and drug resistance in the human pathogen Candida albicans
Résumé
Drug resistance and cellular adhesion are two key elements of both dissemination and prevalence of the human
fungal pathogen Candida albicans. Smi1 belongs to a family of hub proteins conserved among the fungal kingdom
whose functions in cellular signaling affect morphogenesis, cell wall synthesis and stress resistance. The data
presented here indicate that C. albicans SMI1 is a functional homolog of Saccharomyces cerevisiae KNR4 and is
involved in the regulation of cell wall synthesis. Expression of SMI1 in S. cerevisiae knr4Δ null mutants rescued
their sensitivity to caspofungin and to heat stress. Deletion of SMI1 in C. albicans resulted in sensitivity to the
cell-wall-perturbing compounds Calcofluor White and Caspofungin. Analysis of wild-type and mutant cells by
Atomic Force Microscopy showed that the Young’s Modulus (stiffness) of the cell wall was reduced by 85% upon
deletion of SMI1, while cell surface adhesion measured by Force Spectroscopy showed that the surface expression
of adhesive molecules was also reduced in the mutant. Over-expression of SMI1, on the contrary, increased
cell surface adhesion by 6-fold vs the control strain. Finally, Smi1-GFP localized as cytoplasmic patches
and concentrated spots at the sites of new cell wall synthesis including the tips of growing hyphae, consistent
with a role in cell wall regulation. Thus, Smi1 function appears to be conserved across fungi, including the yeast
S. cerevisiae, the yeast and hyphal forms of C. albicans and the filamentous fungus Neurospora crassa.
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