Candida albicans is a commensal fungus inhabiting the gastrointestinal (GI) tract of >60% of humans. It can however cause serious, life-threatening systemic infections in people immunocompromised or otherwise seriously ill. The source of these infections is most often the endogenous C. albicans living in the patient’s own GI tract. Despite antifungal intervention, 40% of systemic C. albicans infections are lethal. Understanding how C. albicans is kept in check through competition with the GI microbiota is therefore important. The most commonly used mouse model of C. albicans GI commensalism involves treating mice with a cocktail of antibiotics, precluding the ability to introduce and study the effects of human GI microbiota on C. albicans colonisation. We have therefore developed a novel, in vitro colon model to allow us to study the effects of human GI microbiota on C. albicans.
In order to characterise our in vitro colon model, 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. We also carried out transcriptomic analyses comparing C. albicans gene expression in our in vitro colon model to that in two parts of the mouse GI tract. Consistent with recent in vivo findings, we observed the expression of key hypha-specific “virulence” genes in our in vitro colon model, despite C. albicans growing in the yeast morphology. This supports a role for the products of these hypha-associated “virulence” genes in commensalism.
Overall, the similarities and differences identified through these two comparative studies have allowed us to define where our in vitro colon model sits relative to the mouse model of GI commensalism. This will be considered as we take our investigations forward and examine the effect of human GI microbiota on C. albicans in a colon-simulating environment, with a view to identifying potentially therapeutic bacterial species residing in the GI tract of humans.