While C. albicans has largely been studied as a pathogen, its primary role is a commensal of the gastrointestinal tract. Overall, the fungal components of the GI microbiome are less well studied than the bacterial members, despite fungi making up a significant portion of the commensal microbiota. Understanding C. albicans’ role in the GI niche will provide important insights into fungal GI commensalism.
My studies investigate the role that filamentation plays in gut commensalism. C. albicans filamentation has previously been characterized as an important part of the pathogenic lifestyle of the fungus, but the role of hyphae in GI commensalism is unclear. We show that the C. albicans filamentation program is detrimental to commensal colonization, as mutants of pro-filamentation transcription factors are hyperfit in the gut. Interestingly, however, we find that hyphae are present throughout the gut. Because hyphae themselves are not detrimental to commensalism, we hypothesize that expression of hyphal specific genes mediates regulation of the commensal population. Indeed, we find that mutants of hyphal specific cell surface proteins, like Sap6, are hyperfit in the GI tract, suggesting that cell type specific markers, rather than cell shape, mediate commensal fitness.
We also find that C. albicans’ interactions with other members of the microbiota, namely Lactobacilli, are important mediators of commensal fitness. Our lab previously discovered a novel phenotypic form of C. albicans, termed GUT cells, which are specialized for commensalism. Surprisingly, mice naturally colonized with high levels of Lactobacillus spp. antagonize the GUT cell commensal advantage. GUT cells, which are normally less responsive to classic filamentation cues as compared to white cells, filament robustly in the presence of Lactobacillus species in vitro. As we know that filamentation is detrimental to commensal, we hypothesized that Lactobacillus-GUT cell interactions reverse the competitive advantage of GUT cells. Indeed, we find that pre-colonizing mice with high levels of Lactobacillus, antagonizes recovery of GUT cells from GI tract.
Taken together, these studies help us understand how C. albicans phenotypic transitions and interactions with other members of the gut microbiota influence commensal colonization in the mammalian GI tract.