{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T05:54:05Z","timestamp":1771912445171,"version":"3.50.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2013,6,25]],"date-time":"2013-06-25T00:00:00Z","timestamp":1372118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2013,8,30]],"date-time":"2013-08-30T00:00:00Z","timestamp":1377820800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2013,8,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In the human fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            , 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\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            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 \u03b2-glucans. To prove that these phenotypes occurred due to serine\/leucine exchange, the\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            adhesin and invasin\n            <jats:italic>ALS3<\/jats:italic>\n            was expressed in\n            <jats:named-content content-type=\"genus-species\">Saccharomyces cerevisiae<\/jats:named-content>\n            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\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            due to its potential to generate cell surface variability, which significantly alters fungus-host interactions.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The translation of genetic information into proteins is a highly accurate cellular process. In the human fungal pathogen\n            <jats:named-content content-type=\"genus-species\">Candida albicans<\/jats:named-content>\n            , 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\n            <jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>\n            virulence attributes, such as morphogenesis, phenotypic switching, and adhesion. Here, we show that CUG mistranslation masks the fungal cell wall molecule \u03b2-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.\n          <\/jats:p>","DOI":"10.1128\/mbio.00285-13","type":"journal-article","created":{"date-parts":[[2013,6,26]],"date-time":"2013-06-26T00:32:29Z","timestamp":1372206749000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":84,"title":["Candida albicans CUG Mistranslation Is a Mechanism To Create Cell Surface Variation"],"prefix":"10.1128","volume":"4","author":[{"given":"Isabel","family":"Miranda","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Ana","family":"Silva-Dias","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Rita","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Rita","family":"Teixeira-Santos","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Carolina","family":"Coelho","sequence":"additional","affiliation":[{"name":"Center for Neurosciences and Cell Biology, University of Coimbra and Faculty of Medicine, Coimbra, Portugal"}]},{"given":"Teresa","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Center for Neurosciences and Cell Biology, University of Coimbra and Faculty of Medicine, Coimbra, Portugal"}]},{"given":"Manuel A. S.","family":"Santos","sequence":"additional","affiliation":[{"name":"RNA Biology Laboratory, Department of Biology and Centre for Environmental and Marine Studies (CESAM), University of Aveiro, Aveiro, Portugal"}]},{"given":"Cid\u00e1lia","family":"Pina-Vaz","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Department of Microbiology, Hospital S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Norma V.","family":"Solis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA"}]},{"given":"Scott G.","family":"Filler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}]},{"given":"Ac\u00e1cio G.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal"},{"name":"Burn Unit and Department of Plastic and Reconstructive Surgery, Hospital S\u00e3o Jo\u00e3o, Porto, 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