High throughput RNA sequencing of C. albicans colonizing the murine GI tract reveals a role for a secreted effecter in commensalism

Candida albicans is a human gut commensal and an opportunistic pathogen. The ability to transition from yeasts to invasive hyphae is a central virulence attribute, but it is unclear how these two cell types function during commensal growth.  Using FISH to visualize C. albicans in a murine gut colonization model, we observed the co-occurrence of yeasts and hyphae throughout the gastrointestinal tract. Forward genetic analysis revealed that major transcriptional activators of yeast-to-hypha morphogenesis have unexpected activity as potent inhibitors of commensalism.  In vivo FISH, transcriptomic, and genetic analyses indicate that the morphogenesis program inhibits commensal fitness, not through control of cell shape as expected from in vitro studies, but by activating expression of a hypha-specific pro-inflammatory secreted protease and a hyphal cell surface adhesin. These results reveal a tradeoff between fungal programs supporting commensalism and virulence within the commensal niche in which selection against hypha-specific markers limits the disease-causing potential of this ubiquitous commensal-pathogen. WT (control) and ume6 (experimental) C. albicans strains were grown under 3 condtions (YPD 30C, 3 replicates; YPD+10% serum 37C, 3 replicates; and murine large intestine, 5 replicates) and then processed for gene expression analysis