Oral Presentation 15th Lorne Infection and Immunity 2025

Developing novel microbiome-based therapeutics to prevent life-threatening invasive fungal infections (#45)

Bianca Briscas 1 , Matthew Prokop 1 , Harry Tiernan 1 , Isaac Lawrence 1 , Emily Rutten 2 , Remy B Young 2 , Emily Gulliver 2 , Shafagh Waters 3 , Samuel Forster 2 , Megan D Lenardon 1
  1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, NSW, Australia
  2. Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia
  3. School of Biomedical Sciences, University of New South Wales, Kensington, NSW, Australia

Candida albicans is a commensal fungus found in the gastrointestinal (GI) tract of over 80% of adults. However, it is also one of the WHO’s ‘critical group’ fungal priority pathogens. Despite antifungal intervention, the mortality rate of invasive C. albicans infections is over 35%. Combined with increasing antifungal resistance, an alternative strategy to manage these infections is needed.

We have identified human GI bacteria that possess anti-C. albicans activity. Faecal samples were obtained from 27 healthy adult donors and homogenates were co-cultured with C. albicans in an in vitro colon model. Seventeen faecal homogenates that reduced C. albicans colony forming units (CFUs) were identified. 16S rRNA gene sequencing revealed the bacterial composition of the donor faecal microbiota. Multivariate statistical analyses identified 106 bacterial amplicon sequence variants that were statistically significantly associated with the in vitro killing of C. albicans.

To experimentally validate these associations, 39 gut bacterial isolates corresponding to the ASVs associated with anti-C. albicans activity were obtained from the Australian Microbiome Culture Collection. Three gut bacterial isolates which killed C. albicans in our in vitro colon model were selected for further investigation. Multiple isolates of these three gut bacterial species were obtained.

Bacterial culture supernatants inhibited the growth of both a C. albicans lab strain and a C. albicans gut isolate, indicating that products secreted by these gut bacteria inhibit C. albicans growth to varying degrees. Co-culture experiments utilising the Cerillo duet system are being carried out to characterise the dynamics of C. albicans killing. Comparative genomics, metabolomics and proteomics will be carried out to identify the secreted product responsible for C. albicans growth inhibition.

We propose to harness this anti-C. albicans activity and develop a microbiome-based therapeutic which can clear C. albicans from the GI tract of at-risk patients, thereby preventing invasive infections from arising.