Fig. 1. Screen of the BU-CMD library identifies azoffluxin as a fluconazole (FLC) potentiator against C. auris.

a BU-CMD library was screened at 50 μM in the presence or absence of 128 μg/mL of FLC in RPMI medium at 30 °C for 48 h. Growth of C. auris strain VPCI 673/P/12, as determined by optical density at 600 nm (OD₆₀₀), is plotted in the presence of each CMD compound alone and in combination with FLC. Dotted lines represent 7-median absolute deviations from the median for each condition. Red circles indicate compounds that showed significant bioactivity. The shaded quadrant indicates compounds that show enhanced activity in the presence of fluconazole, with azoffluxin shown as a filled red circle. b Checkerboard assays with azoffluxin (CMLD012336) and FLC were performed in RPMI at 30 °C by titering 2-fold dilution series of azoffluxin and FLC. Growth in each well is presented in heat-map format based on the OD₆₀₀ of wells at 48 h relative to the no-drug control (see color bar). The fractional inhibitory concentration index (FICI) was calculated to assess interaction effect, with a value <0.5 indicating synergy. c Structure of CMLD012336 (azoffluxin). d FLC Etest strips in the presence and absence of 50 μM azoffluxin. C. auris cells (1 × 10⁶) C. auris cells were plated on YPD agar, the E-test strip was added, and plates were incubated at 30 °C for 24 h prior to imaging. e Dose-response assay based on 2-fold serial dilution of azoffluxin starting from 50 μM in the absence and presence of indicated concentration of FLC for C. auris Ci6684 (Erg11^Y132F), C. albicans (SN95), C. glabrata (BG2), or S. cerevisiae (BY4741), respectively. The highest FLC concentrations that did not affect growth alone for each species was used. Dose-response assays were incubated for 48 h at 30 °C in RPMI. Growth in each well was quantified by the OD₆₀₀ of treated wells relative to the respective no-drug control (see color bar in b). Source data are provided as a Source Data file.