Candida albicans is a commensal fungus found in the gastrointestinal (GI) tract of over 60% 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 that most often arise from the GI tract is ~ 47%. Combined with increasing antifungal resistance, an alternative strategy to manage invasive C. albicans infections is needed.
We propose that bacteria from the human GI tract with anti-C. albicans activity can be used as a microbial therapeutic to clear C. albicans from the GI tract of at-risk patients, thereby preventing invasive infections from arising.
To identify bacteria in the human GI tract with anti-C. albicans activity, we obtained faecal samples from 27 anonymous, healthy, adult donors. C. albicans was co-cultured with faecal homogenates in an in vitro colon model. Seventeen faecal homogenates thar reduced C. albicans colony forming units (CFUs) (compared to a C. albicans-only control) were identified.
16S rRNA gene sequencing was used to determine the bacterial composition of the faecal microbiota(s). Multivariate statistical analyses allowed us to identify bacterial amplicon sequence variants (ASVs) that were statistically significantly associated with the in vitro killing of C. albicans.
To experimentally validate these associations, gut bacterial isolates that correspond to the ASVs associated with anti-C. albicans activity were obtained (n=39). So far, 19 have reduced C. albicans CFUs compared to the control, therefore demonstrating their ability to inhibit C. albicans growth in colon-simulating conditions.
Future work will include investigating the mechanisms by which these bacterial isolates kill C. albicans. Overall, this work supports the premise of using microbiome-based intervention for invasive C. albicans infections in a way that will circumvent the threat of rising antimicrobial resistance.