Antifungal drug resistance in Candida glabrata: role of cellular signaling and gene regulatory networks.

Nakaseomyces glabratus (Candida glabrata) is an opportunistic human fungal pathogen of high priority that shares an ancestor with the non-pathogenic yeast Saccharomyces cerevisiae. Candida glabrata causes infections of the mucosal surfaces as well as fatal deep-seated tissue infections in immunocompromised individuals. The co-resistance to two commonly used antifungal drug classes, azoles and echinocandins, is increasingly being reported in clinical isolates of C. glabrata all over the world, which poses a significant threat to the successful treatment of C. glabrata infections. Acquisition of drug resistance in hospital settings is a complex multifaceted process that is governed by various factors including antimicrobial stewardship. This review summarizes both the key clinical antifungal resistance mechanisms, and the contribution of cellular stress signaling pathways to drug resistance acquisition in C. glabrata. Specifically, we discuss the emerging concepts regarding the role of mitochondrial functions, epigenetic modifications, and the host niche in the development of drug resistance. Lastly, we outline some potential areas for future research that will enable us to better understand the drug evolutionary dynamics of this important human fungal pathogen.