Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

• Tipo: Artigo em Revista Científica Internacional
• Data: 2013

Autores

Isabel Miranda (Autor) FMUP; Ana Dias (Autor) FMUP; Rita Rocha (Autor) FMUP; Rita Santos (Autor) FMUP; Carolina Coelho (Autor) Outra; Teresa Gonçalves (Autor) Outra; Manuel AS Santos (Autor) Outra; Cidália Vaz (Autor) FMUP; Norma V Solis (Autor) Outra; Scott G Filler (Autor) Outra; Acácio Rodrigues (Autor) FMUP

Revista

Título: mBio

Vol. 4 Nº 4

Página Inicial: e00285

ISSN: 2161-2129

Editora: American Society for Microbiology

Indexação

ISI Web of Knowledge - 72 Citações

Scopus - 73 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Ciências da saúde

Outras Informações

ID Authenticus: P-008-DNV

DOI: 10.1128/mbio.00285-13

Abstract (EN): 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 beta-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. IMPORTANCE The translation of genetic information into proteins is a highly accurate cellular process. In the human fungal pathogen Candida albicans, a unique mistranslation event involving the CUG codon occurs. The CUG codon is mainly translated as serine but can also be translated as leucine. Leucine and serine are two biochemically distinct amino acids, hydrophobic and hydrophilic, respectively. The increased rate of leucine incorporation at CUG decoding triggers C. albicans virulence attributes, such as morphogenesis, phenotypic switching, and adhesion. Here, we show that CUG mistranslation masks the fungal cell wall molecule beta-glucan that is normally recognized by the host immune system, delaying its response. Furthermore, we demonstrate that two different proteins of the adhesin Als3 generated by CUG mistranslation confer increased hydrophobicity and adhesion ability on yeast cells. Thus, CUG mistranslation functions as a mechanism to create protein diversity with differential activities, constituting an advantage for a mainly asexual microorganism. This could explain its preservation during evolution.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9