Virulence traits and differential translocation of gut-derived Candida albicans

Abstract

Candida albicansis an opportunistic pathogenic yeast commonly found as part of the gut microbiome, which is thought to be the major reservoir of C. albicans in humans. The ability of C. albicans to adhere to, invade and damage epithelium, along with subsequent escape from the gut lumen into the bloodstream, can lead to life-threatening disseminated fungal infections. Examining the interactions of C. albicans with the intestinal epithelial barrier is vital to understanding its ability to disseminate and cause systemic infections. A set of seven C. albicans strains (six of gut origin: one healthy donor, one cancer patient, one Crohn’s disease patient and three unknown health status; alongside ‘non-gut’ reference strain SC5314) was profiled for virulence traits. C. albicans strains were profiled for biofilm formation (crystal violet staining), hyphal formation (microscopy) and cytotoxicity (lactate dehydrogenase release; during coculture with confluent Caco-2 gut epithelial cells). Additionally, the ability of C. albicans strains to translocate across epithelial cell layers was assessed during coculture with differentiated Caco-2 monolayers on Transwell™ permeable supports. Common virulence traits of hyphal formation and cytotoxicity were reduced in gut C. albicanscompared to non-gut reference strain SC5314, while biofilm formation compared to SC5314 was variable. Translocation assays revealed that gut strains of C. albicans are capable of translocating across Caco-2 epithelial cell layers in greater numbers than non-gut reference strain SC5314, with the highest levels of translocation observed from a Crohn’s disease isolate. These insights suggest that gut-specific adaptations may influence luminal escape and pathogenicity of C. albicans.