Time course analysis of Candida albicans metabolites during biofilm development

Biofilm-associated infections are difficult to treat because of their decreased susceptibility to antimicrobial therapy. Candida albicans is the most common fungal pathogen associated with colonization and biofilm formation on the surfaces of indwelling medical devices which show intrinsic resistance to many commonly used antifungal agents. In this study, a metabonomic method using gas chromatography-mass spectrometry (GC/MS) was developed to characterize metabolic profiles during the whole biofilm developmental phases compared to the planktonic mode in C. albicans. Thirty-one differentially produced metabolites between the biofilm and planktonic specimens at each time point were identified, and they were mainly involved in the tricarboxylic acid (TCA) cycle, lipid synthesis, amino acid metabolism, glycolysis, and oxidative stress. Further experiments showed that lack of trehalose, one of the metabolites differentially produced between biofilm and planktonic cells, resulted in abnormal biofilm formation and increased sensitivity to amphotericin B and miconazole. This study provides a systemic view of the metabolic pattern during the development of C. albicans biofilms, indicating that multicomponent, phase-specific mechanisms are operative in the process of biofilm formation.