Effects of fluconazole on the metabolomic profile of Candida albicans

Aspasia Katragkou, Elizabeth L. Alexander, Hyungjin Eoh, Saki K. Raheem, Emmanuel Roilides, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

Background: Little is known about the effects of fluconazole on the metabolism of Candida albicans. We performed LC/MS-based metabolomic profiling of the response of C. albicans cells to increasing doses of fluconazole. Methods: C. albicans cells were cultured to mid-logarithmic growth phase in liquid medium and then inoculated in replicate on to nitrocellulose filters under vacuum filtration. Organisms were cultured to mid-logarithmic growth phase and treated with 0-4 mg/L fluconazole. Following metabolic quenching at mid-logarithmic growth phase, intracellular metabolites were extracted and analysed by LC/MS. Changes in pool sizes of individual metabolites were verified by Student's t-test, adjusted for multiple hypothesis testing by Benjamini-Hochberg correction. Distribution of metabolites was analysed by the Kyoto Encyclopedia of Genes and Genomes metabolic pathways database. Results: We reproducibly detected 64 metabolites whose identities were confirmed by comparison against a pure standard and a library of accurate mass-retention time pairs. These 64 metabolites were broadly representative of eukaryotic central metabolic pathways. Among them 12 had their mean abundance significantly altered in response to increasing fluconazole concentrations. Pool sizes of four intermediates of central carbon metabolism (α-ketoglutarate, glucose-6-phosphate, phenylpyruvate and ribose-5-phosphate) and mevalonate were increased by 0.5-1.5-fold (P ≤ 0.05). Five amino acids (glycine, proline, tryptophan, aminoisobutanoate and asparagine) and guanine were decreased by 0.5-0.75-fold (P ≤ 0.05). Conclusions: Fluconazole treatment of C. albicans resulted in increased central carbon and decreased amino acid synthesis intermediates, suggesting a rerouting of metabolic pathways. The function of these metabolomic changes remains to be elucidated; however, they may represent previously unrecognized mechanisms of metabolic injury induced by fluconazole against C. albicans.

Original languageEnglish (US)
Article numberdkv381
Pages (from-to)635-640
Number of pages6
JournalThe Journal of antimicrobial chemotherapy
Volume71
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

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Metabolomics
Fluconazole
Candida albicans
Metabolic Networks and Pathways
Carbon
Growth
Encyclopedias
Amino Acids
Mevalonic Acid
Glucose-6-Phosphate
Collodion
Asparagine
Guanine
Vacuum
Proline
Tryptophan
Glycine
Libraries
Cultured Cells
Genome

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Katragkou, A., Alexander, E. L., Eoh, H., Raheem, S. K., Roilides, E., & Walsh, T. J. (2016). Effects of fluconazole on the metabolomic profile of Candida albicans. The Journal of antimicrobial chemotherapy, 71(3), 635-640. [dkv381]. https://doi.org/10.1093/jac/dkv381

Effects of fluconazole on the metabolomic profile of Candida albicans. / Katragkou, Aspasia; Alexander, Elizabeth L.; Eoh, Hyungjin; Raheem, Saki K.; Roilides, Emmanuel; Walsh, Thomas J.

In: The Journal of antimicrobial chemotherapy, Vol. 71, No. 3, dkv381, 01.03.2016, p. 635-640.

Research output: Contribution to journalArticle

Katragkou, A, Alexander, EL, Eoh, H, Raheem, SK, Roilides, E & Walsh, TJ 2016, 'Effects of fluconazole on the metabolomic profile of Candida albicans', The Journal of antimicrobial chemotherapy, vol. 71, no. 3, dkv381, pp. 635-640. https://doi.org/10.1093/jac/dkv381
Katragkou A, Alexander EL, Eoh H, Raheem SK, Roilides E, Walsh TJ. Effects of fluconazole on the metabolomic profile of Candida albicans. The Journal of antimicrobial chemotherapy. 2016 Mar 1;71(3):635-640. dkv381. https://doi.org/10.1093/jac/dkv381
Katragkou, Aspasia ; Alexander, Elizabeth L. ; Eoh, Hyungjin ; Raheem, Saki K. ; Roilides, Emmanuel ; Walsh, Thomas J. / Effects of fluconazole on the metabolomic profile of Candida albicans. In: The Journal of antimicrobial chemotherapy. 2016 ; Vol. 71, No. 3. pp. 635-640.
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