Discovery of a new chemical scaffold for the treatment of superbug <i>Candida auris</i> infections
Jie Tu, Tianbao Zhu, Qingwen Wang, Wanzhen Yang, Yahui Huang, Defeng Xu, Na Liu, Chunquan Sheng
Abstract
Candida auris 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 A1 showed potent in vitro and in vivo efficacy against Candida auris infection. Mechanism investigation revealed that compound A1 blocked the biosynthesis of virulence factors and fungal cell walls through the inhibition of glycosylphosphatidylinositol (GPI) and GPI-anchored proteins. Thus, compound A1 represents a promising lead compound to combat drug-resistant candidiasis.