Fig 3.

Impact of the seven 1,4-benzodiazepines (1,4-BZD)/fluconazole (FLC) drug combinations on FLC susceptibility, tolerance, and cell survival of Candida albicans. Compounds were screened using FLC (25 µg) disk diffusion assays on YPD plates containing 100 µM 1,4-BZDs or the same volume of DMSO (vehicle). Panels show FLC susceptibility (RAD₅₀ and RAD₂₀, (A) and tolerance [fraction of growth at 20% drug inhibition (FoG₂₀), (B)] following 48 hours of growth. After 48 hours, FLC disks were replaced with glucose disks (G, 8 mg), grown for an additional 48 hours, and susceptibility and tolerance were quantified again. Heatmaps show average values for three or more biological replicates. (C–D) Checkerboard assays showing the impact of drug combinations of FLC (starting at 128 µg/mL) with the seven 1,4-BZDs and sortin2 (starting at 100 µM) on FLC susceptibility (MIC₉₀, C) and tolerance (SMG, D) for C. albicans isolates SC5314, SP-945, and P60002. (E) FICI₉₀ scores for combinations of potentiators and FLC based on MIC₉₀ values. Left-side table indicates the type of FLC-potentiator interaction based on the FICI score. Heatmap shows average values from three to four biological replicates.