Genotypic, Proteomic, and Phenotypic Approach to Decipher the Response to Caspofungin Drug and Calcineurin Inhibitors in Echinocandin-Resistant Candida glabrata

Echinocandin resistance is a great concern, considering that these drugs are recommended as first-line therapy for invasive candidiasis. Our objective at the genomic level was to identify resistance mechanisms by sequencing echinocandin-resistant C. glabrata; we found a genetic variation (F659del) in the FKS2 gene associated exclusively with resistant C. glabrata strains. On the other hand, proteomics data revealed that some up-regulated proteins were involved in cell wall biosynthesis, response to stress and pathogenesis (37 genes were recognized as members of the calmodulin-calcineurin pathway). In conclusion, our findings confirmed that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening fungal infectious diseases.