Regulation of Candida albicans Als adhesins in inflammatory environments 4310

Abstract Description Candida albicans is a polymorphic commensal fungus that colonizes mucosal sites within the human body, including the intestinal tract. While harmless in most individuals, it can cause life-threatening disseminated infections in immunocompromised hosts and exacerbate inflammatory bowel disease. The ability of C. albicans to cause disease and inflammation has been shown by numerous groups to be associated with its expression of the adhesin proteins, Als1 and Als3. Als1 and Als3 have been shown to be important in adhesion and invasion of intestinal epithelial cells. Our lab has previously shown that strains highly expressing Als1 and Als3 are selected against for colonization of the intestines during homeostasis. While we know these are critical proteins for driving disease and inflammation, we do not know how the expressions of Als1 and Als3 are regulated and how their expression may be altered in an inflamed environment. Using mouse models of colitis, bulk RNA sequencing, and a novel anti-fungal vaccine, we hypothesize that expression of Als1 and Als3 may be upregulated in an inflamed environment and that immune components such as secretory IgA may be regulating their expression. Preliminary data suggest that peak inflammation correlates with increased Als3 expression, highlighting its potential role of exacerbating inflammation. Our data also suggests that vaccinating mice with an anti-Als3 based vaccine may reduce fungal burden and disease severity. Funding Sources NIH DP2AI177927 NIH 3DP2AI177927-02S1 NIH R21AI188719 Crohns and Colitis Foundation-Career development award University of Colorado start up funds Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)