Discovery of a new chemical scaffold for the treatment of superbug <i>Candida auris</i> infections

<i>Candida auris</i> has emerged as a serious threat of public health and caused global epidemic due to multi-drug resistance, remarkable transmissibility and high mortality. To tackle the challenging super fungus, novel benzoanilide antifungal agents were discovered by an integrated strategy of phenotypic screen, hit optimization, antifungal assays and mechanism exploration. The most promising compound <b>A1</b> showed potent <i>in vitro</i> and <i>in vivo</i> efficacy against <i>Candida auris</i> infection. Mechanism investigation revealed that compound <b>A1</b> blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound <b>A1</b> represents a promising lead compound to combat drug-resistant candidiasis.