Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Fungal IP7-protein interaction and invasive fungal disease: a dangerous liaison (#199)

Julianne T Djordjevic 1 2 , Sophia Lev 1 2
  1. Centre for Infectious Diseases & Microbiology , Westmead Institute for Medical Research, 176 Hawkesbury Rd, Westmead NSW 2145, Sydney, NSW, Australia
  2. Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia

Invasive fungal diseases (IFDs) affect 300 million people and cause >1.5 million deaths annually, matching deaths from tuberculosis and exceeding those from malaria. A major factor contributing to the high morbidity and mortality is that only a few antifungal drug classes have been developed, the therapeutic effect of which is compromised by poor bioavailability, poor efficacy and/or toxicity. We have discovered a novel strategy for antifungal drug therapy by demonstrating that the inositol polyphosphate signalling molecule, IP7, is critical for IFD. Using the model pathogen Cryptococcus neoformans, we showed that IP7 is produced by the phospholipase C/inositol polyphosphate kinase (IPK) pathway. Blocking IP7 production by inhibiting IPKs is feasible, as IPK-selective inhibitors have already been generated. To develop IPK inhibitors into antifungal drugs, a better understanding of how IP7 promotes IFD is essential. I will discuss how we are addressing this key gap in knowledge, opening the door to developing a novel class of antifungal agent.