Poster Presentation 16th Lorne Infection and Immunity 2026

I want to break free: A metabolic cross-talk between immune cells and fungal pathogens determines their fate upon interaction   (132545)

Harshini Weerasinghe 1 , Orawan Tulyaprawat 1 , Helen Stölting 1 2 , Johannes Sonnberger 3 , Joshua Nickson 1 , Theresa Lange 3 , Bryce van Denderen 1 , Tricia L Lo 1 , Francios A.B Olivier 1 , Cathrine Hall 4 , John Silke 4 , James E Vince 4 5 , Kate E Lawlor 4 6 7 , Stefan Bröer 8 , Bernhard Hube 3 9 10 , Thomas Naderer 1 , Adam J Rose 2 , Ana Traven 1
  1. Department of Biochemistry and Molecular Biology and the Infection Program, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC
  2. Department of Biochemistry and Molecular Biology and the Metabolism, Diabetes and Obesity Program, Biomedicine Discovery Institute, Monash University, Clayton 3800, VIC
  3. Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute (HKI), Jena, Germany
  4. The Walter and Eliza Hall Institute of Medical Research, Parkville 3010, VIC
  5. The Department of Medical Biology, University of Melbourne, Parkville 3010, VIC, Australia
  6. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, , Clayton 3800, VIC, Australia
  7. Department of Molecular and Translational Science, Monash University, Clayton, VIC
  8. Research School of Biology, Australian National University, Canberra 0200, AUSTRALIAN CAPITAL TERRITORY, Australia
  9. Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany
  10. Institute of Microbiology, Friedrich Schiller University, Jena, Germany

Opportunistic fungal pathogens that cause human disease cause about 3.7 million deaths annually and are a grave threat to human health. The rapid emergence of drug resistant pathogenic fungialong with the overuse and inadequacies of commercially available antifungal drugs, have meant that our therapeutic safety net for fungal infections has become limited. Recently, the study of immunometabolism (how immune cells remodel their metabolism when challenged by fungal pathogens) during fungal infection, has offered insights into host-pathogen metabolic crosstalk, as well as potential for innovation in antifungal treatments. We have previously shown that both Candida albicans and Candida auris infections cause a metabolic switch driven by high glucose consumption in macrophages, the immune phagocytes that are key players in antifungal innate immunity. Both pathogens utilise the metabolic switch to escape immune containment, outcompete, starve and kill macrophages. For C. albicans infection, glucose starvation of macrophages triggers an NLRP3 inflammasome response and the resulting secretion of the pro-inflammatory cytokine IL-b as a warning signal to the rest of the immune system. Conversely, C. auris isolates are able to kill macrophages while suppressing the NLRP3 responseIn this talk I will present our findings investigating the cell death mechanisms that cause Candida-responsive glucose dependent cell death. We have identified the executor of this program and have uncovered metabolites that act to inhibit this cell death pathway, significantly rescuing macrophages. These metabolites could prove to be valuable as therapeutic interventions to improve patient outcomes.