Discovery of a new chemical scaffold for the treatment of superbug Candida auris infections

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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Candida auris; benzoanilide; antifungal; drug resistance; Candida albicans

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All the data including experimental procedures, synthetic methods, structural characterization and spectra data are available in the supplementary information files.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (Grants 81725020 to C.S., 82003591 to J. T., and 81973175 to N. L.), the Innovation Program of Shanghai Municipal Education Commission (Grant 2019-01-07-00-07-E00073 to C.S.) and Science and Technology Commission of Shanghai Municipality (Grant 20S11900400 to C.S.).