Dr Megan Lenardon

Opportunistic invasive fungal pathogens cause over 6.5 million life-threatening infections and 3.75 million deaths per year worldwide. The number of deaths per year is greater than those attributed to either tuberculosis, malaria, or breast cancer or prostate cancer. Bloodstream infections caused by Candida species (candidaemia) are one of the most frequent life-threatening invasive fungal infections, with the majority caused by one species, Candida albicans.

C. albicans colonises the gut of most healthy individuals but does not usually cause serious disease because the physical barriers between our gut and the bloodstream, combined with our immune defences and the suppressive powers of the indigenous gut microbiota, prevent these infections. However, this opportunistic pathogen can cause serious, life-threatening disseminated disease when these barriers and defences are compromised (e.g. seriously ill patients in the ICU, during cancer chemotherapy or immunotherapy, organ/stem cell transplantation, or when the gut microbiota is disturbed), which renders us vulnerable to infections from the C. albicans that colonises our gut. It is estimated that there are >1.5 million cases of candidaemia and invasive candidiasis per year worldwide, with a treated mortality rate of 35% and untreated mortality rate of >95%. There is an urgent clinical need for the development of diagnostics and new therapies for invasive candidiasis which research in my group aims to address in innovative ways.

Cell wall structure and biosynthesis. I have been studying the cell and molecular biology of C. albicans for almost 20 years and have developed specific expertise in the biosynthesis of the C. albicans cell wall and its structure. My postdoctoral research was focussed on the regulation of the synthesis of chitin, an essential structural polysaccharide found in the cell wall almost all pathogenic fungi, but is not found in humans, and so represents an attractive target for antifungal drugs. Utilising state-of-the-art imaging techniques, I have investigated the precise ultrastructure of the C. albicans cell wall. These methods include high pressure freezing/freeze substitution, transmission electron microscopy and electron tomography. Determining precisely how the cell wall components are arranged, and how their arrangement changes as cells encounter different conditions, has informed the understanding of the innate and adaptive immune responses to fungi.

Gut fungi. I study the interactions between anaerobic gut bacteria and C. albicans with a view to developing microbiome-based therapeutics to prevent life-threatening infections from occurring.

Development of antifungal polymers. In collaboration with Prof. Cyrille Boyer in the School of Chemical Sciences and Engineering at UNSW, and Dr Sascha Brunke at the HKI in Jena, Germany, we are developing novel antifungal polymers which resemble antimicrobial peptides with antifungal activity and determining their mode of action.