Author(s):
Miranda, Isabel ; Silva-Dias, Ana ; Rocha, Rita ; Teixeira-Santos, Rita ; Coelho, Carolina ; Gonçalves, Teresa M. ; Santos, Manuel A. S. ; Pina-Vaz, Cidália ; Solis, Norma V ; Filler, Scott G ; Rodrigues, Acácio G
Date: 2013
Persistent ID: https://hdl.handle.net/10316/109751
Origin: Estudo Geral - Universidade de Coimbra
Subject(s): Animals; Antigens, Fungal; Candida albicans; Cell Line; Fungal Proteins; Host-Pathogen Interactions; Leucine; Macrophages; Membrane Proteins; Mice; Phagocytosis; Recombinant Proteins; Saccharomyces cerevisiae; Serine; Antigenic Variation; Protein Biosynthesis
Description
In the human fungal pathogen Candida albicans, the CUG codon is translated 97% of the time as serine and 3% of the time as leucine, which potentially originates an array of proteins resulting from the translation of a single gene. Genes encoding cell surface proteins are enriched in CUG codons; thus, CUG mistranslation may influence the interactions of the organism with the host. To investigate this, we compared a C. albicans strain that misincorporates 28% of leucine at CUGs with a wild-type parental strain. The first strain displayed increased adherence to inert and host molecules. In addition, it was less susceptible to phagocytosis by murine macrophages, probably due to reduced exposure of cell surface β-glucans. To prove that these phenotypes occurred due to serine/leucine exchange, the C. albicans adhesin and invasin ALS3 was expressed in Saccharomyces cerevisiae in its two natural isoforms (Als3p-Leu and Als3p-Ser). The cells with heterologous expression of Als3p-Leu showed increased adherence to host substrates and flocculation. We propose that CUG mistranslation has been maintained during the evolution of C. albicans due to its potential to generate cell surface variability, which significantly alters fungus-host interactions.
