Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans

Rose E. Jeeves, Robert P. Mason, Alexandra Woodacre, Annette M. Cashmore

Research output: Contribution to JournalArticle

Abstract

The pathogenic yeast Candida albicans possesses a reductive iron uptake system which is active in iron-restricted conditions. The sequestration of iron by this mechanism initially requires the reduction of free iron to the soluble ferrous form, which is catalysed by ferric reductase proteins. Reduced iron is then taken up into the cell by a complex of a multicopper oxidase protein and an iron transport protein. Multicopper oxidase proteins require copper to function and so reductive iron and copper uptake are inextricably linked. It has previously been established that Fre10 is the major cell surface ferric reductase in C. albicans and that transcription of FRE10 is regulated in response to iron levels. We demonstrate here that Fre10 is also a cupric reductase and that Fre7 also makes a significant contribution to cell surface ferric and cupric reductase activity. It is also shown, for the first time, that transcription of FRE10 and FRE7 is lower in hyphae compared to yeast and that this leads to a corresponding decrease in cell surface ferric, but not cupric, reductase activity. This demonstrates that the regulation of two virulence determinants, the reductive iron uptake system and the morphological form of C. albicans, are linked.
Original languageEnglish
Pages (from-to)629-644
Number of pages16
JournalYeast
Volume28
Issue number9
DOIs
Publication statusE-pub ahead of print - 21 Jun 2011

Fingerprint

Hyphae
Candida albicans
Iron
Yeasts
Genes
Oxidoreductases
Copper
ferric citrate iron reductase
Protein Transport
Virulence
Carrier Proteins
Proteins

Keywords

  • Candida
  • Ferric reductases
  • Hyphal growth
  • Iron and copper uptake
  • Transcriptional regulation

Cite this

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abstract = "The pathogenic yeast Candida albicans possesses a reductive iron uptake system which is active in iron-restricted conditions. The sequestration of iron by this mechanism initially requires the reduction of free iron to the soluble ferrous form, which is catalysed by ferric reductase proteins. Reduced iron is then taken up into the cell by a complex of a multicopper oxidase protein and an iron transport protein. Multicopper oxidase proteins require copper to function and so reductive iron and copper uptake are inextricably linked. It has previously been established that Fre10 is the major cell surface ferric reductase in C. albicans and that transcription of FRE10 is regulated in response to iron levels. We demonstrate here that Fre10 is also a cupric reductase and that Fre7 also makes a significant contribution to cell surface ferric and cupric reductase activity. It is also shown, for the first time, that transcription of FRE10 and FRE7 is lower in hyphae compared to yeast and that this leads to a corresponding decrease in cell surface ferric, but not cupric, reductase activity. This demonstrates that the regulation of two virulence determinants, the reductive iron uptake system and the morphological form of C. albicans, are linked.",
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Ferric reductase genes involved in high-affinity iron uptake are differentially regulated in yeast and hyphae of Candida albicans. / Jeeves, Rose E.; Mason, Robert P.; Woodacre, Alexandra; Cashmore, Annette M.

In: Yeast, Vol. 28, No. 9, 21.06.2011, p. 629-644.

Research output: Contribution to JournalArticle

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