• Potential ß (1-3)-Glucan Unmasking Genes for Drug Targeting in Candida albicans to Promote Detection by Innate Immune Cells

      Hasim, Sahar; Patel, Sonny; Shankar, Arthi (2021)
      Growing resistance, toxicity, and side effects to current antifungal agents have generated a strong need for further therapeutic developments. Candida albicans are the most common causes of human fungal infections, and they include painful, oral, and vaginal mucosal infections and lethal, invasive bloodstream infections. A key factor for recognizing Candida albicans by Dectin-1 receptor in immune cells is the detection of ß (1-3)-glucan found in the inner cell wall. However, the fungus decreases the efficiency of immune detection by covering ß (1-3)-glucan with a layer of mannosylated glycoproteins, referred to as masking. This study aims to find the gene(s) that enhance ß (1-3)-glucan exposure, leading to increased recognition of Candida albicans by macrophages. We screened several cell wall mutants for unmasking by staining each cell with ß (1-3)-glucan antibody and showing the decreased mannan level by staining with concanavalin A. Overall, our data demonstrated primary evidence suggesting that mutants mnn10?/?, mnn9?/?, and orf19.3869?/?, in Candida albicans showed unmasking in the presence of sublethal caspofungin concentration (50 ng/ml), which promotes the detection by innate immune cells. These genes could serve as potential drug targets that can be used to have synergy when combined with caspofungin against Candida albicans.