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

Abstract

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.

Integrated proteomic and metabolomic analysis to study the effects of spaceflight on Candida albicans

“…Proteomics [9] could explore the expression of all the proteins of C. albicans under different environmental conditions. Metabolomics [10] is the study of the composition and variation of metabolic groups, thereby revealing the overall metabolic response and dynamic changes under different conditions. Thus, the results of integrated omics analysis could be useful for understanding the molecular mechanism of C. albicans with the rapid proliferation and enhanced toxicity under the space environment.…”

Metabolic profiling of Candida clinical isolates of different species and infection sources

“…In this study, the highest concentrations of aspartate, lysine and creatinine were observed in respiratory tract, blood and vagina isolates, respectively. Aspartate is an amino acid associated with virulence and stress due to the exposure to antifungals 20 .…”

Catch the wave: Metabolomic analyses in human pathogenic fungi

“…Another major aim of metabolic studies in pathogenic fungi is to gain deeper insight in the effect of antifungal agents. Metabolomics-based approaches have been used, for example, to examine the effects of fluconazole on C. albicans metabolism [21,22]. The drug increased the abundance of central carbon metabolism intermediates (e.g., glucose-6-phosphate, phenylpyruvate, α-ketoglutarate), whereas intermediates of amino acid and purine metabolism were decreased [21].…”