<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

ABSTRACT 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 cod...

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Autores principales:	Isabel Miranda, Ana Silva-Dias, Rita Rocha, Rita Teixeira-Santos, Carolina Coelho, Teresa Gonçalves, Manuel A. S. Santos, Cidália Pina-Vaz, Norma V. Solis, Scott G. Filler, Acácio G. Rodrigues
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fb54dfcfd35a419eb47b4a2c35574587
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spelling	oai:doaj.org-article:fb54dfcfd35a419eb47b4a2c355745872021-11-15T15:43:08Z<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation10.1128/mBio.00285-132150-7511https://doaj.org/article/fb54dfcfd35a419eb47b4a2c355745872013-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00285-13https://doaj.org/toc/2150-7511ABSTRACT 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. 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 β-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.Isabel MirandaAna Silva-DiasRita RochaRita Teixeira-SantosCarolina CoelhoTeresa GonçalvesManuel A. S. SantosCidália Pina-VazNorma V. SolisScott G. FillerAcácio G. RodriguesAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 4 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Isabel Miranda Ana Silva-Dias Rita Rocha Rita Teixeira-Santos Carolina Coelho Teresa Gonçalves Manuel A. S. Santos Cidália Pina-Vaz Norma V. Solis Scott G. Filler Acácio G. Rodrigues <named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
description	ABSTRACT 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. 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 β-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.
format	article
author	Isabel Miranda Ana Silva-Dias Rita Rocha Rita Teixeira-Santos Carolina Coelho Teresa Gonçalves Manuel A. S. Santos Cidália Pina-Vaz Norma V. Solis Scott G. Filler Acácio G. Rodrigues
author_facet	Isabel Miranda Ana Silva-Dias Rita Rocha Rita Teixeira-Santos Carolina Coelho Teresa Gonçalves Manuel A. S. Santos Cidália Pina-Vaz Norma V. Solis Scott G. Filler Acácio G. Rodrigues
author_sort	Isabel Miranda
title	<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
title_short	<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
title_full	<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
title_fullStr	<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
title_full_unstemmed	<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation
title_sort	<named-content content-type="genus-species">candida albicans</named-content> cug mistranslation is a mechanism to create cell surface variation
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/fb54dfcfd35a419eb47b4a2c35574587
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<named-content content-type="genus-species">Candida albicans</named-content> CUG Mistranslation Is a Mechanism To Create Cell Surface Variation

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