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Table 1.

HILIC-QQQ/MS scan parameters.

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Table 1 Expand

Fig 1.

Variations of MIC values of FCZ, MCZ and KCZ for the C. albicans strain SC5314 grown in medium containing twice their most recently measured MIC of FCZ.

The result showed that the increase in fluconazole MIC was accompanied by a corresponding increase in resistance to miconazole and ketoconazole.

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Fig 1 Expand

Fig 2.

The typical total ions current chromatograms.

(A&B)Intracellular sample separated on UHPLC-Q-TOF/MS in positive and negative ionization mode; (C&D)Extracellular sample separated on UHPLC-Q-TOF/MS in positive and negative ionization mode; (E)Intracellular sample separated on GC-MS; (F)Extracted ion chromatography on HILIC-QQQ/MS.

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Fig 2 Expand

Fig 3.

PLS-DA scores plot of intracellular metabolites from GC-MS.

(A)S group vs R group; (B)S group vs S+KCZ group; (C)R group vs R+KCZ group; (D)S+KCZ group vs R+KCZ group.

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Fig 3 Expand

Fig 4.

PLS-DA scores plot of intracellular metabolites from LC-Q-TOF/MS.

(A)S group vs R group; (B)S group vs S+KCZ group; (C)R group vs R+KCZ group; (D)S+KCZ group vs R+KCZ group.

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Fig 4 Expand

Fig 5.

PLS-DA scores plot of extracellular metabolites from LC-Q-TOF/MS.

(A)S group vs R group; (B)S group vs S+KCZ group; (C)R group vs R+KCZ group; (D)S+KCZ group vs R+KCZ group.

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Fig 5 Expand

Table 2.

The number of differential metabolites from each model.

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Table 2 Expand

Table 3.

Related metabolites and their metabolic pathway.

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Table 3 Expand

Fig 6.

Heatmap of glycerophospholipid from HILIC-QQQ/MS.

Colors represent fold change in the metabolite concentration in different groups. Red indicates increased concentration levels of metabolites; green indicates decreased concentration levels of metabolites.

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Fig 6 Expand

Table 4.

The result of total number of carbons in the fatty acid chains of phosphoglyceride.

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Table 4 Expand

Table 5.

The result of odd chain fatty acid of phosphoglyceride.

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Table 5 Expand

Fig 7.

Schematic overview of the main differences in the metabolite change associated with drug resistance of Candida albicans.

The differentially produced metabolites are mainly involved in amino metabolism, sphingolipid metabolism, TCA cycle, oxidative stress, glutathione metabolism and lipid metabolism. Metabolites in red marks are only related to drug stress; metabolites in blue marks are only related to strain type or drug resistance level; metabolites marked green are associated with the three described above.

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Fig 7 Expand