Fungal Kinases With a Sweet Tooth: Pleiotropic Roles of Their Phosphorylated Inositol Sugar Products in the Pathogenicity of Cryptococcus neoformans Present Novel Drug Targeting Opportunities

Frontiers in Cellular and Infection Microbiology

Cecilia Li²  Adolfo Saiardi³  Desmarini Desmarini⁴  Julianne T. Djordjevic⁴  Sophie Lev⁴  Tania C. Sorrell⁴ 

[1] Centre for Infectious Diseases and Microbiology, The Westmead Institute for Medical Research, Sydney, NSW, Australia;Centre for Infectious Diseases and Microbiology–Public Health, NSW Health Pathology, Westmead Hospital, Sydney, NSW, Australia;MRC Laboratory for Molecular Cell Biology, University College London, London, United Kingdom;Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia;Sydney Medical School-Westmead, The University of Sydney, Sydney, NSW, Australia;

关键词: inositol polyphosphate kinase;    inositol pyrophosphate;    IP7;    IP;    PP-IP;    virulence;   

DOI  :  10.3389/fcimb.2019.00248

来源: DOAJ

【 摘 要 】

Invasive fungal pathogens cause more than 300 million serious human infections and 1.6 million deaths per year. A clearer understanding of the mechanisms by which these fungi cause disease is needed to identify novel targets for urgently needed therapies. Kinases are key components of the signaling and metabolic circuitry of eukaryotic cells, which include fungi, and kinase inhibition is currently being exploited for the treatment of human diseases. Inhibiting evolutionarily divergent kinases in fungal pathogens is a promising avenue for antifungal drug development. One such group of kinases is the phospholipase C1-dependent inositol polyphosphate kinases (IPKs), which act sequentially to transfer a phosphoryl group to a pre-phosphorylated inositol sugar (IP). This review focuses on the roles of fungal IPKs and their IP products in fungal pathogenicity, as determined predominantly from studies performed in the model fungal pathogen Cryptococcus neoformans, and compares them to what is known in non-pathogenic model fungi and mammalian cells to highlight potential drug targeting opportunities.

【 授权许可】

Unknown