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Updated: Mar 6, 2026

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Inhibiting Mrt4-rRNA interaction with fumaramidmycin-based derivatives as an antifungal strategy

Hongxuan Cao1, Jie Tu2, Jiahui Chen3

  • 1State Key Laboratory of Green Pesticide, College of Chemistry, Central China Normal University, Wuhan, China.

Nature Communications
|March 4, 2026
PubMed

Insights

A new antifungal compound selectively targets fungal ribosome assembly, showing strong efficacy against drug-resistant fungi like Candida auris. This discovery offers a promising strategy against challenging fungal infections.

Area of Science:

  • Biochemistry
  • Mycology
  • Medicinal Chemistry

Background:

  • Growing antifungal drug resistance and treatment limitations necessitate novel therapeutic approaches.
  • Ribosome assembly is a critical process for fungal survival and a potential drug target.

Purpose of the Study:

  • To develop novel cis-fumaramidmycin-derived analogs targeting fungal ribosome assembly factor Mrt4.
  • To identify and characterize a potent antifungal agent effective against drug-resistant fungal strains, including Candida auris.

Main Methods:

  • Antifungal screening and lead identification.
  • Active-and-inactive-based protein profiling (AIBPP), chemical-genetic profiling, and fluorescence polarization assays.
  • In vivo efficacy studies in Galleria mellonella larvae and murine candidiasis models.

Main Results:

  • A lead compound, 20, demonstrated potent activity against multiple drug-resistant fungi, including Candida auris.
  • Compound 20 selectively inhibits the interaction between Candida albicans Mrt4 (CaMrt4) and rRNA by covalently engaging C96 and C189, disrupting fungal ribosomal assembly.
  • Compound 20 showed therapeutic efficacy in both insect and mammalian infection models.

Conclusions:

  • cis-fumaramidmycin-derived analogs represent a viable strategy for combating drug-resistant fungal infections.
  • Selective inhibition of CaMrt4-rRNA interaction by compound 20 offers a new therapeutic avenue.
  • This research provides a much-needed potential treatment for the increasing burden of fungal infections.

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