Candida albicans is a commensal fungus inhabiting the gastrointestinal (GI) tract of more than 60% of humans. It is normally kept in check through the gut epithelium, immune cells, and competition with GI bacteria. When these barriers are disrupted, C. albicans can escape the gut and cause systemic infections, resulting in sepsis and death. Understanding how C. albicans is kept commensal by the GI microbiota is therefore of critical importance. The most commonly used mouse model of C. albicans GI commensalism involves treating mice with a cocktail of antibiotics, precluding the ability to introduce human GI microbiota. We have therefore developed a novel, in vitro model that simulates the human colon microenvironment and facilitates the introduction of human GI microbiota.
In order to characterise our in vitro colon model, we compared the transcriptome of C. albicans after incubation in our model to that in standard lab conditions. We then compared gene expression in our model to that in two parts of the mouse GI tract from publicly available datasets. Further, we designed, optimised, and carried out competitive fitness assays utilising deletion mutants for five genes, WOR1, EFG1, ECE1, CRZ2, and SAP6, the deletion or overexpression of which had been shown to affect the commensal fitness of C. albicans in the mouse GI tract. In line with recent findings, we highlight the surprisingly important role in colonisation and commensalism of genes that were previously – under standard laboratory conditions – described as “hypha-associated”.
Having characterised the behaviour of C. albicans in our in vitro model in the absence of human GI microbiota, future work will address the question of how the behaviour of C. albicans changes in response to co-culturing with the human GI microbiota in our in vitro model. We expect that the generated knowledge will allow us to exploit the human GI microbiota in the development of novel therapeutic strategies to combat systemic C. albicans infections.