Li, C; Lev, S; Saiardi, A; Desmarini, D; Sorrell, TC; Djordjevic, JT; (2016) Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery. Journal of Fungi , 2 (3) , Article 24. 10.3390/jof2030024.

Preview

Text Inositol Polyphosphate Kinases, Fungal Virulence and Drug Discovery.pdf - Published Version Download (1MB) | Preview

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.

Download activity - last month

Export as XMLJSONCSV

Download activity - last 12 months

Export as JSONXMLCSV

Downloads by country - last 12 months

Export as CSVJSONXML

Archive Staff Only

View Item