Candida albicans is a commensal fungus that resides in the gastrointestinal (GI) tract of over 60% of adults. However, it is also one of the WHO’s four critical group fungal priority pathogens, capable of causing superficial and life-threatening invasive fungal infections in humans. Invasive infections arise from the C. albicans colonising the GI tract, and even with antifungal intervention, mortality is as high as 47%. An alternative strategy to manage invasive C. albicans infections is required.
Microbiome-based therapeutics are emerging as a novel approach to disease management and prevention. Bacteria within the human GI tract that have anti-C. albicans activity exist[1]. These anti-Candida bacteria could form the basis of a microbial therapeutic to clear C. albicans from the GI tract of at-risk patients, preventing infection by removing the source.
To identify bacteria with anti-C. albicans activity, we obtained faecal samples from 27 anonymous, healthy, adult donors (UNSW Human Ethics Approval HC210301). C. albicans was co-cultured with faecal homogenate from each donor sample in an in vitro colon model[1]. A log reduction in C. albicans colony forming units (CFUs) > 2 (compared to the C. albicans-only control) was observed for 17 donor faecal samples which we defined as antagonistic, while the remaining 10 samples were defined as benign.
16S rRNA gene sequencing was used to characterise the bacterial composition of the faecal microbiota(s) before and after coculture with C. albicans. Antagonistic microbiota profiles clustered together after 48 h coculture (p = 0.01, ANOSIM). Subsequent analyses using LEfSe[2] identified specific bacterial amplicon sequence variants (ASVs) that were statistically significantly associated with antagonism – i.e., the in vitro killing of C. albicans.
To experimentally validate these statistical associations, 52 gut bacterial isolates from the Australian Microbiome Culture Collection (AusMiCC) that correspond to the ASVs associated with anti-C. albicans activity have been identified. These will be screened against C. albicans in our in vitro colon model. We have also established the conditions required for C. albicans to colonise air-exposed, fully differentiated mucous-producing organoids in a Transwell[3] so that we can test whether the bacterial isolates can clear C. albicans ex vivo.