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.
Highlights
Human fungal pathogens are a serious, but often neglected threat to human health
A number of recent studies have shown that perturbation of phosphate acquisition in both C. albicans and C. neoformans impacts on virulence in a range of infection models
This is an exciting time in the phosphate homeostasis field
Summary
It is estimated that fungal infections are responsible for over one million human deaths per annum [1] Most of these fungi-attributed deaths are due to either Cryptococcus, Candida, or Aspergillus species which primarily affect immunocompromised patients. A. fumigatus is responsible for over 200,000 cases of invasive aspergillosis each year in immunocompromised hosts, which is associated with alarming mortality rates of 50% at best [1] This fungus causes chronic pulmonary aspergillosis, a gradual destructive disease in the lung, which is estimated to affect 3 million people worldwide [1]. A number of recent studies have shown that perturbation of phosphate acquisition in two of the major human fungal pathogens, Candida albicans and Cryptococcus neoformans, attenuates virulence in a range of infection models. We summarized the current data supporting the necessity of phosphate acquisition in mediating the virulence of human fungal pathogens
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