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

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

doi:10.1111/mmi.13722

Stavroula L Kastora, Carol A Munro + Show 3 more

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https://doi.org/10.1111/mmi.13722

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Journal: Molecular microbiology	Publication Date: Jun 19, 2017
Citations: 20	License type: CC BY 4.0

Affiliation: University of Aberdeen

Abstract

SummaryThe 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.

Highlights

Of the circa 1.5 million fungal species thought to inhabit our planet, only around 600 have been reported to be pathogenic for humans
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
SFP1 is induced in stressed glucose-grown cells, whereas RTG3 is upregulated in stressed lactate-grown cells

Summary

Introduction

Of the circa 1.5 million fungal species thought to inhabit our planet, only around 600 have been reported to be pathogenic for humans. Transcript profiling studies that have examined the in vivo gene expression patterns of C. albicans cell populations from the blood or internal organs suggest that both glycolytic and gluconeogenic pathways are active in these fungal populations (Andes et al, 2005; Fradin et al, 2005; Barelle et al, 2006; Walker et al, 2008) This counterintuitive finding could be explained either by an ability of individual C. albicans cells to express both pathways simultaneously (Sandai et al, 2012; Childers et al, 2016) or by the complexity of host niches, in which individual C. albicans cells can be exposed to glucose-containing or glucose-lacking microenvironments depending on their location (Hube, 2004; Barelle et al, 2006; Miramon et al, 2012). Most dietary sugars are absorbed in the small intestine before

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