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The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor
Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previousl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305457/ https://www.ncbi.nlm.nih.gov/pubmed/22438810 http://dx.doi.org/10.1371/journal.ppat.1002592 |
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author | Mayer, François L. Wilson, Duncan Jacobsen, Ilse D. Miramón, Pedro Große, Katharina Hube, Bernhard |
author_facet | Mayer, François L. Wilson, Duncan Jacobsen, Ilse D. Miramón, Pedro Große, Katharina Hube, Bernhard |
author_sort | Mayer, François L. |
collection | PubMed |
description | Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31) elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine. |
format | Online Article Text |
id | pubmed-3305457 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33054572012-03-21 The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor Mayer, François L. Wilson, Duncan Jacobsen, Ilse D. Miramón, Pedro Große, Katharina Hube, Bernhard PLoS Pathog Research Article Candida albicans is the most frequent cause of oral fungal infections. However, the exact pathogenicity mechanisms that this fungus employs are largely unknown and many of the genes expressed during oral infection are uncharacterized. In this study we sought to functionally characterize 12 previously unknown function genes associated with oral candidiasis. We generated homozygous knockout mutants for all 12 genes and analyzed their interaction with human oral epithelium in vitro. Eleven mutants caused significantly less epithelial damage and, of these, deletion of orf19.6656 (DUR31) elicited the strongest reduction in pathogenicity. Interestingly, DUR31 was not only involved in oral epithelial damage, but in multiple stages of candidiasis, including surviving attack by human neutrophils, endothelial damage and virulence in vivo. In silico analysis indicated that DUR31 encodes a sodium/substrate symporter with 13 transmembrane domains and no human homologue. We provide evidence that Dur31 transports histatin 5. This is one of the very first examples of microbial driven import of this highly cytotoxic antimicrobial peptide. Also, in contrast to wild type C. albicans, dur31Δ/Δ was unable to actively increase local environmental pH, suggesting that Dur31 lies in the extracellular alkalinization hyphal auto-induction pathway; and, indeed, DUR31 was required for morphogenesis. In agreement with this observation, dur31Δ/Δ was unable to assimilate the polyamine spermidine. Public Library of Science 2012-03-15 /pmc/articles/PMC3305457/ /pubmed/22438810 http://dx.doi.org/10.1371/journal.ppat.1002592 Text en Mayer et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mayer, François L. Wilson, Duncan Jacobsen, Ilse D. Miramón, Pedro Große, Katharina Hube, Bernhard The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title | The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title_full | The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title_fullStr | The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title_full_unstemmed | The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title_short | The Novel Candida albicans Transporter Dur31 Is a Multi-Stage Pathogenicity Factor |
title_sort | novel candida albicans transporter dur31 is a multi-stage pathogenicity factor |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3305457/ https://www.ncbi.nlm.nih.gov/pubmed/22438810 http://dx.doi.org/10.1371/journal.ppat.1002592 |
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