Fig. 4: Antifungal activity of coniotin A against C. albicans and multidrug-resistant C. auris.

a Coniotin A (CNA) synergizes with caspofungin (CAP) in Candida species. Checkerboard assays depicted as heatmaps show the average growth of biological duplicates, normalized to controls without compounds. The potentiation of coniotin A and caspofungin was evaluated against C. auris CBS12775 and C. albicans ATCC90028. Relative growth is depicted by color, as indicated by the scale bar in the bottom right. Fractional Inhibitory Concentration Index (FICI) values, calculated as described in the Methods, are shown in the top right corner of each checkerboard. FICI values below 0.5 denote synergistic interactions. b Rapid assessment of the therapeutic potential of coniotin A using a high-throughput Caenorhabditis elegans–C. albicans infection model. C. elegans were infected with C. albicans ATCC90028 and treated with various concentrations of coniotin A. Representative images show worms treated with DMSO (i, negative control), 1 µg/mL coniotin A (ii), and 8 µg/mL coniotin A (iii). Scale bar = 0.2 mm. Experiments were independently repeated three times with similar results. c Survival of C. elegans infected with C. auris CBS 12775 and treated with amphotericin B (AMB), coniotin A (CNA), or vehicle (DMSO). Twenty-five worms per condition were monitored over 48 h in three biologically independent experiments. Survival curves were analyzed using the Kaplan–Meier method. Statistical significance was assessed by a two-sided Log-rank (Mantel–Cox) test (χ² = 39.48, df = 1, p < 0.0001), with confirmation by the Gehan–Breslow–Wilcoxon test (χ² = 28.64, p < 0.0001), comparing CNA (1× MIC) treatment to the DMSO control group. d Proteolytic stability of coniotin A compared to LL-37 in the presence of trypsin (Try), neutrophil elastase (Ela), and human serum (HS). Peptides (40 μM) were incubated with trypsin, elastase, or 50% human serum at 37 °C for up to 12 h. Residual intact peptide was quantified by HR LC-MS and normalized to the untreated control (0 h). Data represent mean ± SD from three independent experiments. Figure 4c, d, Source data and full statistical results are provided as a Source Data file.