Phosphate theft: a path to fungal pathogenic success
Julianne T Djordjevic A B and Sophie Lev AA Centre for Infectious Diseases and Microbiology, Westmead Millennium Institute, 176 Hawkesbury Road, Westmead, NSW 2145, Australia
B Corresponding author. Tel: + 61 2 8627 3420, Email: julianne.djordjevic@sydney.edu.au
Microbiology Australia 36(2) 49-52 https://doi.org/10.1071/MA15018
Published: 19 March 2015
Abstract
Inorganic phosphate/PO43–/Pi is an essential and major 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. To become 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 consisting of Pi transporters, Pi mobilising 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.
References
[1] Park, B.J. et al. (2009) Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS. AIDS 23, 525–530.| Estimation of the current global burden of cryptococcal meningitis among persons living with HIV/AIDS.Crossref | GoogleScholarGoogle Scholar | 19182676PubMed |
[2] Chayakulkeeree, M. et al. (2008) Role and mechanism of phosphatidylinositol-specific phospholipase C in survival and virulence of Cryptococcus neoformans. Mol. Microbiol. 69, 809–826.
| 1:CAS:528:DC%2BD1cXhtVehurzK&md5=4a429df9187cda2fdffe206f55212129CAS | 18532984PubMed |
[3] Cox, G.M. et al. (2001) Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans. Mol. Microbiol. 39, 166–175.
| Extracellular phospholipase activity is a virulence factor for Cryptococcus neoformans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlvVSmtA%3D%3D&md5=14c405524287f1b8f9156fae9c0c9b4bCAS | 11123698PubMed |
[4] Coelho, C. et al. (2014) The tools for virulence of Cryptococcus neoformans. Adv. Appl. Microbiol. 87, 1–41.
| The tools for virulence of Cryptococcus neoformans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtVWktLvL&md5=fffd2ff198a2486cb375b9b865e2b703CAS | 24581388PubMed |
[5] Lev, S. et al. (2014) Identification of Aph1, a phosphate-regulated, secreted, and vacuolar acid phosphatase in Cryptococcus neoformans. mBio 5, e01649-14.
| Identification of Aph1, a phosphate-regulated, secreted, and vacuolar acid phosphatase in Cryptococcus neoformans.Crossref | GoogleScholarGoogle Scholar | 25227465PubMed |
[6] Kretschmer, M. et al. (2014) Defects in phosphate acquisition and storage influence virulence of Cryptococcus neoformans. Infect. Immun. 82, 2697–2712.
| Defects in phosphate acquisition and storage influence virulence of Cryptococcus neoformans.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVWmu7jP&md5=d2ce949e3a1baaf113fdd6475e9b3ac1CAS | 24711572PubMed |
[7] Lee, Y.S. et al. (2008) Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate. Nat. Chem. Biol. 4, 25–32.
| Molecular basis of cyclin-CDK-CKI regulation by reversible binding of an inositol pyrophosphate.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsVegtbbN&md5=bd35518502957e26cb7fe9f95e9fd102CAS | 18059263PubMed |
[8] Lee, Y.S. et al. (2007) Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates. Science 316, 109–112.
| Regulation of a cyclin-CDK-CDK inhibitor complex by inositol pyrophosphates.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjvVarsLg%3D&md5=3bce7e92384082b44991c767c6ed0910CAS | 17412959PubMed |
[9] Lonetti, A. et al. (2011) Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases. J. Biol. Chem. 286, 31 966–31 974.
| Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFCju7%2FI&md5=3d87e1cc8655358b5db7397167138a2fCAS |
[10] Vidotto, V. et al. (2006) Extracellular enzymatic activities in Cryptococcus neoformans strains isolated from AIDS patients in different countries. Rev. Iberoam. Micol. 23, 216–220.
| Extracellular enzymatic activities in Cryptococcus neoformans strains isolated from AIDS patients in different countries.Crossref | GoogleScholarGoogle Scholar | 17388645PubMed |
[11] Wightman, R.M. and Haynes, C.L. (2004) Synaptic vesicles really do kiss and run. Nat. Neurosci. 7, 321–322.
| Synaptic vesicles really do kiss and run.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXisFCisrw%3D&md5=9cd3b2d827fdf95d058bddd345ea8e48CAS | 15048116PubMed |
[12] Lev, S. et al. (2013) Phospholipase C of Cryptococcus neoformans regulates homeostasis and virulence by providing inositol trisphosphate as a substrate for Arg1 kinase. Infect. Immun. 81, 1245–1255.
| Phospholipase C of Cryptococcus neoformans regulates homeostasis and virulence by providing inositol trisphosphate as a substrate for Arg1 kinase.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXlt1SltLs%3D&md5=a5704a13e6afdec773696baba5a02c9eCAS | 23381992PubMed |