Sfp1 and Rtg3 reciprocally modulate carbon source-conditional stress adaptation in the pathogenic yeast Candida albicans

Stavroula L. Kastora, Carmen Herrero De Dios, Gabriela M Avelar, Carol A Munro, Alistair J. P. Brown

Research output: Contribution to journalArticle

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Abstract

The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host-imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these 'non-standard' growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source-conditional manner. SFP1 is induced in stressed glucose-grown cells, whereas RTG3 is upregulated in stressed lactate-grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source-dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)620-636
Number of pages17
JournalMolecular Microbiology
Volume105
Issue number4
Early online date19 Jun 2017
DOIs
Publication statusPublished - Aug 2017

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Candida
Candida albicans
Yeast
Carbon
Yeasts
Growth
Lactic Acid
Glucose
Temperature
Carboxylic Acids
Virulence
Transcription Factors
Cell growth
Genes

Keywords

  • Stress adaptation
  • oxidative stress
  • cationic stress
  • osmotic stress
  • nitrosative stress
  • carbon source
  • RTG3
  • SFP1
  • Candida albicans

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Sfp1 and Rtg3 reciprocally modulate carbon source-conditional stress adaptation in the pathogenic yeast Candida albicans. / Kastora, Stavroula L.; Herrero De Dios, Carmen; Avelar, Gabriela M; Munro, Carol A; Brown, Alistair J. P.

In: Molecular Microbiology, Vol. 105, No. 4, 08.2017, p. 620-636.

Research output: Contribution to journalArticle

Kastora, Stavroula L. ; Herrero De Dios, Carmen ; Avelar, Gabriela M ; Munro, Carol A ; Brown, Alistair J. P. / Sfp1 and Rtg3 reciprocally modulate carbon source-conditional stress adaptation in the pathogenic yeast Candida albicans. In: Molecular Microbiology. 2017 ; Vol. 105, No. 4. pp. 620-636.
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note = "Acknowledgements We thank Aaron Mitchell, Dominique Sanglard and Suzanne Noble for their generosity in providing mutant collections, and Linghuo Jiang for generously providing strains. We also thank Susan Budge for her support and excellent technical assistance. We also thank the qPCR Facility in the Institute of Medical Sciences, and particularly Fiona Saunders for her great advice and help. SLK was supported by a PhD scholarship from the University of Aberdeen. AJPB was supported by the UK Biotechnology and Biological Research Council (BB/F00513X/1; BB/K017365/1), by the European Research Council (STRIFE Advanced Grant; ERC-2009-AdG-249793), and by the UK Medical Research Council (MR/M026663/1). AJPB and CAM were also supported by the Wellcome Trust (088858; 097377), and by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).",
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AU - Brown, Alistair J. P.

N1 - Acknowledgements We thank Aaron Mitchell, Dominique Sanglard and Suzanne Noble for their generosity in providing mutant collections, and Linghuo Jiang for generously providing strains. We also thank Susan Budge for her support and excellent technical assistance. We also thank the qPCR Facility in the Institute of Medical Sciences, and particularly Fiona Saunders for her great advice and help. SLK was supported by a PhD scholarship from the University of Aberdeen. AJPB was supported by the UK Biotechnology and Biological Research Council (BB/F00513X/1; BB/K017365/1), by the European Research Council (STRIFE Advanced Grant; ERC-2009-AdG-249793), and by the UK Medical Research Council (MR/M026663/1). AJPB and CAM were also supported by the Wellcome Trust (088858; 097377), and by the MRC Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1).

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N2 - The pathogenicity of the clinically important yeast, Candida albicans, is dependent on robust responses to host-imposed stresses. These stress responses have generally been dissected in vitro at 30°C on artificial growth media that do not mimic host niches. Yet host inputs, such as changes in carbon source or temperature, are known to affect C. albicans stress adaptation. Therefore, we performed screens to identify novel regulators that promote stress resistance during growth on a physiologically relevant carboxylic acid and at elevated temperatures. These screens revealed that, under these 'non-standard' growth conditions, numerous uncharacterised regulators are required for stress resistance in addition to the classical Hog1, Cap1 and Cta4 stress pathways. In particular, two transcription factors (Sfp1 and Rtg3) promote stress resistance in a reciprocal, carbon source-conditional manner. SFP1 is induced in stressed glucose-grown cells, whereas RTG3 is upregulated in stressed lactate-grown cells. Rtg3 and Sfp1 regulate the expression of key stress genes such as CTA4, CAP1 and HOG1 in a carbon source-dependent manner. These mechanisms underlie the stress sensitivity of C. albicans sfp1 cells during growth on glucose, and rtg3 cells on lactate. The data suggest that C. albicans exploits environmentally contingent regulatory mechanisms to retain stress resistance during host colonisation. This article is protected by copyright. All rights reserved.

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