Factors Supporting Cysteine Tolerance and Sulfite Production in Candida albicans.

Détails

ID Serval
serval:BIB_2B93088B96AC
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Factors Supporting Cysteine Tolerance and Sulfite Production in Candida albicans.
Périodique
Eukaryotic Cell
Auteur(s)
Hennicke F., Grumbt M., Lermann U., Ueberschaar N., Palige K., Böttcher B., Jacobsen I.D., Staib C., Morschhäuser J., Monod M., Hube B., Hertweck C., Staib P.
ISSN
1535-9786 (Electronic)
ISSN-L
1535-9786
Statut éditorial
Publié
Date de publication
2013
Volume
12
Numéro
4
Pages
604-613
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The amino acid cysteine has long been known to be toxic at elevated levels for bacteria, fungi, and humans. However, mechanisms of cysteine tolerance in microbes remain largely obscure. Here we show that the human pathogenic yeast Candida albicans excretes sulfite when confronted with increasing cysteine concentrations. Mutant construction and phenotypic analysis revealed that sulfite formation from cysteine in C. albicans relies on cysteine dioxygenase Cdg1, an enzyme with similar functions in humans. Environmental cysteine induced not only the expression of the CDG1 gene in C. albicans, but also the expression of SSU1, encoding a putative sulfite efflux pump. Accordingly, the deletion of SSU1 resulted in enhanced sensitivity of the fungal cells to both cysteine and sulfite. To study the regulation of sulfite/cysteine tolerance in more detail, we screened a C. albicans library of transcription factor mutants in the presence of sulfite. This approach and subsequent independent mutant analysis identified the zinc cluster transcription factor Zcf2 to govern sulfite/cysteine tolerance, as well as cysteine-inducible SSU1 and CDG1 gene expression. cdg1Δ and ssu1Δ mutants displayed reduced hypha formation in the presence of cysteine, indicating a possible role of the newly proposed mechanisms of cysteine tolerance and sulfite secretion in the pathogenicity of C. albicans. Moreover, cdg1Δ mutants induced delayed mortality in a mouse model of disseminated infection. Since sulfite is toxic and a potent reducing agent, its production by C. albicans suggests diverse roles during host adaptation and pathogenicity.
Pubmed
Web of science
Création de la notice
03/05/2013 20:37
Dernière modification de la notice
03/03/2018 15:25
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