Poster Presentation Australian Society for Microbiology Annual Scientific Meeting 2016

Inositol pyrophosphate PP-IP5 is crucial for the metabolic adaptation of Cryptococcus neoformans to the host environment and for its dissemination to the central nervous system (#41)

Cecilia Li 1 , Sophia Lev 1 , Adolfo Saiardi 2 , Desmarini Desmarini 1 , Tania Sorrell 1 3 4 , Julianne Djordjevic 1 3 4
  1. The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
  2. Medical Research Council Laboratory for Molecular Cell Biology, University College London, Gower Street WC1E 6BT London UK, London, UK
  3. Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, NSW, Australia
  4. Westmead Hospital, Westmead, NSW, Australia

Cryptococcus neoformans (C. neoformans) predominantly infects immunocompromised individuals and is the most common cause of fungal meningitis worldwide. It is responsible for causing approximately 1 million new cases of infection and ~500, 000 deaths each year in AIDS patients alone. Fungal factors responsible for the dissemination of C. neoformans from the lungs (primary site of infection) to the central nervous system (CNS) are poorly understood. For C. neoformans to establish a productive lung infection, and subsequently disseminate to the CNS, it must adjust its metabolism to an environment depleted of glucose. Using a combination of gene deletion analysis, HPLC-based metabolic profiling, in vitro assays, RNA-seq and a mouse model of cryptococcosis, we have identified and characterised a novel signalling pathway in C. neoformans. This pathway consists of a series of sequentially acting inositol polyphosphate kinases (IPKs) that convert the simplest inositol polyphosphate signalling molecule, IP3, to the more complex pyrophosphate, PP-IP5. We found that cryptococcal mutant strains lacking PP-IP5 could not utilise simple carbon sources as well as the wild-type strain, and failed to disseminate to the CNS. Studies into the mechanism of action of PP-IP5 in fungal metabolism are ongoing and will be discussed.