Candida albicans strains adapted to the mouse gut are resistant to bile salts via a Flo8-dependent mechanism.

Abstract

Candidaalbicans normally colonizes the human gastrointestinal tract as a commensal. Studying fungal factors involved in colonizing the mammalian gastrointestinal tract requires mouse models with altered microbiota. We have obtained strains of C.albicans through microevolution in the mouse gut for a prolonged period (one year) that display a substantial increase in fitness in this niche. These strains show resistance to bile salts, an increase in their adhesion to the intestinal mucosa, and are unable to filament in response to serum. Genetic analysis revealed some alterations, mainly a triploidy of chr7, a whole chr6 homozygosis, and an SNP in the FLO8 gene (located in the chr6), resulting in a truncated protein version. A wild type FLO8 gene complemented filamentation and bile salt sensitivity but showed an intermediate fitness phenotype in colonization. Alterations in bile salt sensitivity were also evident in bmt mutants, defective in β-mannosylation, and transcriptional targets of Flo8, suggesting a link between the fungal cell wall and mammalian gut colonization via the Flo8 transcriptional regulator.