Phosphate theft: a path to fungal pathogenic success

Abstract

Inorganic phosphate/PO4 /Pi is an essential andmajor constituent of numerous cellular components in all eukaryotes, including fungi. These components include nucleic acids, phospholipids and ATP. Despite its abundance in organic compounds, Pi is relatively scarce in its free form.Tobecome successful pathogens, fungi must therefore acquire free Pi from the host environment via enzyme-mediated hydrolysis of Pi-containing molecules and/or via more efficient use of their own Pi. Fungal adaptation to a Pi-limited environment is governed by the phosphate (PHO) system, a cellular pathway consistingofPi transporters, Pimobilising enzymes and regulatory elements, such as kinases and transcription factors that respond to Pi levels. This system is well studied in the model non-pathogenic yeast, Saccharomyces cerevisiae, but not in fungal pathogens. In this review we present what is known about the PHO system in the model fungal pathogen, Cryptococcus neoformans, including our identification and characterisation of a secreted acid phosphatase, Aph1, which serves as a valuable reporter for identifying the less well-conserved PHO elements, including transcription factors.