Central Carbon Metabolism in Candida albicans Biofilms Is Altered by Dimethyl Sulfoxide
Abstract
:1. Introduction
2. Materials and Methods
2.1. Candida albicans Strain
2.2. Preparation of Inoculum
2.3. Experimental Groups
- (a)
- Control group: cells were cultured in standard MM medium (replicates: C1a, C2a, C3a, C4a, C5a, C1b, C2b, C3b, C4b, C5b, C1c, C2c, C3c, C4c, and C5c).
- (b)
- DMSO group: cells were cultured in MM medium supplemented with 0.03% (v/v) DMSO (replicates: D1a, D2a, D3a, D4a, D5a, D1b, D2b, D3b, D4b, D5b, D1c, D2c, D3c, D4c, and D5c).
2.4. Formation of Aerobic Biofilms under Continuous Flow
2.5. Extraction of Intracellular Metabolites
2.6. Sampling and Quenching (Fixation of Cellular Metabolism)
2.7. Extraction and Quantification of Intracellular Metabolites
2.8. Quantification of Cell Biomass
2.9. Derivatization with Methyl Chloroformate (MCF)
2.10. Gas Chromatography and Mass Spectrometry
2.11. Statistical Analysis
3. Results
3.1. Principal Component Analysis (PCA)
3.2. Metabolite Analysis
3.3. Pathway Activity Profiling (PAPi) Analysis
4. Discussion
4.1. Lipid Metabolism
4.2. Carbon and Carbohydrate Metabolism
4.3. Amino Acid Metabolism
4.4. Cofactors and Vitamins Metabolism
4.5. Energy Metabolism
4.6. Secondary Metabolism
4.7. Final Considerations
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Classification of Metabolites | N° | Intracellular Metabolites |
---|---|---|
Amino acids and their isoforms | 22 | Alanine, asparagine, aspartic acid, beta-alanine, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, norvaline, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine |
Amino acid derivatives | 6 | Creatinine, cystathionine, N-acetylglutamic acid, putrescine, pyroglutamic acid, S-adenosylmethionine |
TCA cycle intermediates | 8 | Alpha-ketoglutaric acid, alpha-ketobutyric acid, cis-aconitic acid, citric acid, fumaric acid, isocitric acid, malic acid, succinic acid |
Fatty acids | 17 | 10,13-dimethyl tetradecanoic acid (10,13-DMTDA), 9-heptadecenoic acid, adipic acid, caprinoic acid, caprylic acid, decanoic acid, docosanoic acid, dodecanoic acid, eicosanoic acid, gamma-linoleic acid, hexanoic acid, myristic acid, palmitelaidic acid, pentadecanoic acid, stearic acid, trans-vaccenic |
Glycolytic intermediates | 2 | 2-phosphoenolpyruvic acid, pyruvic acid |
Cofactors and vitamins | 6 | Dehydroascorbic acid, gamma-aminobutyric acid (GABA), glutathione, NADP/NADPH, nicotinamide, nicotinic acid |
Others | 27 | 1-aminocyclopropane-1-carboxylic acid (ACC), 2-aminoadipic acid, 2-hydroxybutyric acid, 2-isopropylmalic acid, 3-methyl-2-oxopentanoic acid, 4-aminobenzoic acid, 4-hydroxyphenylacetic acid, 4-hydroxyphenylethanol (tyrosol), 5-oxotetrahydrofuran-2- benzoic acid, carbamic acid, carboxylic acid, citramalic acid, dehydroabietic acid, dibutylphthalate (DBP), DL-hydroxyglutaramate, dodecane, EDTA, glutaric acid, glyceric acid, glyoxylic acid, itaconic acid, lactic acid, levulinic acid, malonic acid, oxalic acid, para-toluic acid, quinic acid |
Total no. of identified metabolites | 88 |
Classification of Metabolites | Intracellular Metabolites Altered by DMSO | |
---|---|---|
Upregulated | Downregulated | |
Amino acids and their isoforms | - | Histidine, lysine, methionine, ornithine, threonine, tyrosine |
Amino acid derivatives | N-acetylglutamic acid, putrescine, pyroglutamic acid, S-adenosylmethionine | - |
TCA cycle intermediates | Alpha-ketobutyric acid, alpha-ketoglutaric acid, fumaric acid, malic acid | - |
Fatty acids | 10,13-dimethyl tetradecanoic acid (10,13-DMTDA), dodecanoic acid, myristic acid, stearic acid | - |
Cofactors and vitamins | Dehydroascorbic acid, glutathione | Gamma-aminobutyric acid (GABA) |
Others | 1-aminocyclopropane-1-carboxylic acid (ACC), benzoic acid, dehydroabietic acid, itaconic acid, malonic acid | Carbamic acid |
Total no. of altered metabolites | 19 | 8 |
Metabolic Pathway Groups | Metabolic Pathways Altered by DMSO | |
---|---|---|
Upregulated | Downregulated | |
Amino acid metabolism | Beta-Alanine metabolism D-arginine and D-ornithine metabolism | - |
Lipid metabolism | - | Fatty acid biosynthesis |
Carbohydrate metabolism | - | Pentose phosphate pathway Pentose and glucuronate interconversions Ascorbate and aldarate metabolism |
Carbon metabolism | - | Pyruvate metabolism |
Energy metabolism | Sulphur metabolism | Methane metabolism |
Cofactor and vitamin metabolism | Biotin metabolism Ubiquinone and other terpene-quinones biosynthesis | Vitamin B6 Metabolism |
Secondary metabolites metabolism | Betalain biosynthesis | - |
Total | 6 | 7 |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Arruda, M.F.C.; da Silva Ramos, R.C.P.; de Oliveira, N.S.; Rosa, R.T.; Stuelp-Campelo, P.M.; Bianchini, L.F.; Villas-Bôas, S.G.; Rosa, E.A.R. Central Carbon Metabolism in Candida albicans Biofilms Is Altered by Dimethyl Sulfoxide. J. Fungi 2024, 10, 337. https://doi.org/10.3390/jof10050337
Arruda MFC, da Silva Ramos RCP, de Oliveira NS, Rosa RT, Stuelp-Campelo PM, Bianchini LF, Villas-Bôas SG, Rosa EAR. Central Carbon Metabolism in Candida albicans Biofilms Is Altered by Dimethyl Sulfoxide. Journal of Fungi. 2024; 10(5):337. https://doi.org/10.3390/jof10050337
Chicago/Turabian StyleArruda, Maria Fernanda Cordeiro, Romeu Cassiano Pucci da Silva Ramos, Nicoly Subtil de Oliveira, Rosimeire Takaki Rosa, Patrícia Maria Stuelp-Campelo, Luiz Fernando Bianchini, Silas Granato Villas-Bôas, and Edvaldo Antonio Ribeiro Rosa. 2024. "Central Carbon Metabolism in Candida albicans Biofilms Is Altered by Dimethyl Sulfoxide" Journal of Fungi 10, no. 5: 337. https://doi.org/10.3390/jof10050337