Next Article in Journal
Treatment of Primary Pulmonary Aspergillosis: An Assessment of the Evidence
Next Article in Special Issue
New Horizons in Antifungal Therapy
Previous Article in Journal
PCR Technology for Detection of Invasive Aspergillosis
Article Menu

Export Article

Open AccessReview
J. Fungi 2016, 2(3), 24; doi:10.3390/jof2030024

Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery

1
Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145, Australia
2
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK
3
Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Westmead, NSW 2145, Australia
4
Westmead Hospital, Westmead, NSW 2145, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Maurizio Del Poeta
Received: 22 July 2016 / Revised: 23 August 2016 / Accepted: 30 August 2016 / Published: 6 September 2016
(This article belongs to the Special Issue Novel Antifungal Drug Discovery)
View Full-Text   |   Download PDF [1222 KB, uploaded 6 September 2016]   |  

Abstract

Opportunistic fungi are a major cause of morbidity and mortality world-wide, particularly in immunocompromised individuals. Developing new treatments to combat invasive fungal disease is challenging given that fungal and mammalian host cells are eukaryotic, with similar organization and physiology. Even therapies targeting unique fungal cell features have limitations and drug resistance is emerging. New approaches to the development of antifungal drugs are therefore needed urgently. Cryptococcus neoformans, the commonest cause of fungal meningitis worldwide, is an accepted model for studying fungal pathogenicity and driving drug discovery. We recently characterized a phospholipase C (Plc1)-dependent pathway in C. neoformans comprising of sequentially-acting inositol polyphosphate kinases (IPK), which are involved in synthesizing inositol polyphosphates (IP). We also showed that the pathway is essential for fungal cellular function and pathogenicity. The IP products of the pathway are structurally diverse, each consisting of an inositol ring, with phosphate (P) and pyrophosphate (PP) groups covalently attached at different positions. This review focuses on (1) the characterization of the Plc1/IPK pathway in C. neoformans; (2) the identification of PP-IP5 (IP7) as the most crucial IP species for fungal fitness and virulence in a mouse model of fungal infection; and (3) why IPK enzymes represent suitable candidates for drug development. View Full-Text
Keywords: antifungal compounds; Cryptococcus neoformans; inositol polyphosphate kinases; inositol pyrophosphates; PP-IP5; fungal virulence; cryptococcal meningitis; drug discovery antifungal compounds; Cryptococcus neoformans; inositol polyphosphate kinases; inositol pyrophosphates; PP-IP5; fungal virulence; cryptococcal meningitis; drug discovery
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Li, C.; Lev, S.; Saiardi, A.; Desmarini, D.; Sorrell, T.C.; Djordjevic, J.T. Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery. J. Fungi 2016, 2, 24.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Fungi EISSN 2309-608X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top