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.