Fig 1. A model for the formation of multidrug-resistant strains of C. glabrata.

Long-term exposure to antifungal drugs triggers stress responses that both help maintain cellular integrity in the face of acute stress and promote genomic instability and genetic diversity to facilitate the emergence of genetic variants with enhanced intrinsic resistance. In the case of long-term prophylaxis with azole class drugs in Candida glabrata, this process results in formation of azole-resistant mutants with reduced genome stability. These mutants, when challenged with echinocandin class drugs, rapidly develop echinocandin resistance as well, resulting in formation of multidrug-resistant C. glabrata.