Metabolomic profiling for the identification of potential biomarkers involved in a laboratory azole resistance in Candida albicans

Candida albicans, one of the most common fungal pathogens, is responsible for several yeast infections in human hosts, being resistant to classically used antifungal drugs, such as azole drugs. Multifactorial and multistep alterations are involved in the azole resistance in Candida albicans. In this study, a FCZ-resistant C. albicans strain was obtained by serial cultures of a FCZ-susceptible C. albicans strain in incrementally increasing concentrations of FCZ. We performed an integrated profile of different classes of molecules related to azole resistance in C. albicans by combining several mass-spectrometry based methodologies. The comparative metabolomic study was performed with the sensitive and resistant strains of C.albicans to identify metabolites altered during the development of resistance to fluconazole, while the intervention strains and non-intervention strains of C.albicans to identify metabolites altered involved in cross-resistant to azole drugs. Our analysis of the different metabolites identified molecules mainly involved in metabolic processes such as amino acid metabolism, tricarboxylic acid cycle and phospholipid metabolism. We also compared the phospholipid composition of each group, revealing that the relative content of phospholipids significantly changed during the development of resistance to azole drugs. According with these results, we hypothesized that the metabolism shift might contribute to azole drugs resistance in C.albicans from multifactorial alterations. Our result paves the way to understand processes underlying the resistance to azole drugs in C. albicans, providing the basis for developing new antifungal drugs.