SEMINAR: Eat to Compete - Understanding immunometabolic interactions that drive Candida auris infection

The Centre to Impact AMR's own 2023 Hartland Oration speaker, Dr Harshini Weerasinghe, presented a 45-minute seminar titled 'Eat to Compete: Understanding immunometabolic interactions that drive Candida auris infection'. Harshini spoke about her work on the metabolic interactions of Candida auris with macrophages during infection.

Overview

Opportunistic fungal pathogens that cause human disease pose a serious threat to public health. The rapid emergence of drug resistant pathogenic fungi such as Candida auris, along with the overuse of commercially available antifungal drugs and inadequacies in drug development, 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 significant insights into host-pathogen metabolic crosstalk as well as potential for innovation in antifungal treatments. We investigate the metabolic interactions of C. auris with macrophages during infection. We show that C. auris replicates robustly in macrophages and is able to escape macrophages without killing them. However, after escape, C. auris will outcompete macrophages for nutrients, ultimately resulting in macrophage death without inducing a strong immunological response. We also focus on how macrophages maintain glucose homeostasis to fight off fungal infections and demonstrate that glucose supplementation improves immune-cell outcomes. Our preliminary data suggests that C. auris escapes immune containment by mechanisms that differ from those used by other Candida pathogens and can leverage host metabolic shifts for survival and proliferation.

About the Speaker

Dr Harshini Weerasinghe

Research Fellow, Traven Laboratory, Department of Microbiology

Dr Harshini Weerasinghe has an abiding fascination for all things fungal and scarcely believes it’s taken the TV adaptation of a video game to get the rest of the world just as interested. During her PhD at the University of Melbourne, Harshini investigated the transcriptional dynamics that occur during the interactions of pathogenic fungi and immune system macrophages. And now, within the fungal infection and medical mycology laboratory of Prof. Ana Traven at the Biomedicine Discovery Institute (Monash University), Harshini studies the role of metabolic changes in immune cells and hospital acquired infectious Candida species that drive host-fungal interactions. With the dearth of current antimicrobial drug treatments for fungal infections, Harshini’s work as part of the Centre to Impact AMR is providing unique insights into Candida auris’ strengths and vulnerabilities.

Here's the link to the relevant peer-reviewed journal article discussed during this seminar.