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Microorganisms 2017, 5(3), 48; doi:10.3390/microorganisms5030048

Phosphate Acquisition and Virulence in Human Fungal Pathogens

1,†
,
2,†
and
2,*
1
Oral and Craniofacial Biology, Center of Excellence in Oral Biology, LSUHSC School of Dentistry, New Orleans, LA 70119, USA
2
Institute for Cell and Molecular Biosciences, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 20 July 2017 / Revised: 15 August 2017 / Accepted: 16 August 2017 / Published: 22 August 2017
(This article belongs to the Special Issue Fungal Nutrition Assimilation Strategies and Pathogenicity)
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Abstract

The ability of pathogenic fungi to acquire essential macro and micronutrients during infection is a well-established virulence trait. Recent studies in the major human fungal pathogens Candida albicans and Cryptococcus neoformans have revealed that acquisition of the essential macronutrient, phosphate, is essential for virulence. The phosphate sensing and acquisition pathway in fungi, known as the PHO pathway, has been extensively characterized in the model yeast Saccharomyces cerevisiae. In this review, we highlight recent advances in phosphate sensing and signaling mechanisms, and use the S. cerevisiae PHO pathway as a platform from which to compare the phosphate acquisition and storage strategies employed by several human pathogenic fungi. We also explore the multi-layered roles of phosphate acquisition in promoting fungal stress resistance to pH, cationic, and oxidative stresses, and describe emerging roles for the phosphate storage molecule polyphosphate (polyP). Finally, we summarize the recent studies supporting the necessity of phosphate acquisition in mediating the virulence of human fungal pathogens, highlighting the concept that this requirement is intimately linked to promoting resistance to host-imposed stresses. View Full-Text
Keywords: phosphate homeostasis; PHO pathway; Pho4 transcription factor; Pho80-Pho85 CDK; SPX domains; IP7 inositol polyphosphates; stress resistance; VTC complex; polyphosphate; fungal pathogenesis phosphate homeostasis; PHO pathway; Pho4 transcription factor; Pho80-Pho85 CDK; SPX domains; IP7 inositol polyphosphates; stress resistance; VTC complex; polyphosphate; fungal pathogenesis
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Ikeh, M.; Ahmed, Y.; Quinn, J. Phosphate Acquisition and Virulence in Human Fungal Pathogens. Microorganisms 2017, 5, 48.

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