A marine microbiome antifungal targets urgent-threat drug-resistant fungi

Science. 2020 Nov 20;370(6519):974-978. doi: 10.1126/science.abd6919.

Abstract

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug-resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as C. auris.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Benzopyrans / chemistry
  • Benzopyrans / pharmacology*
  • Benzopyrans / therapeutic use
  • Candida / drug effects*
  • Candidiasis, Invasive / drug therapy*
  • Disease Models, Animal
  • Drug Resistance, Multiple, Fungal*
  • Fungal Proteins / metabolism
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Isoquinolines / therapeutic use
  • Mice
  • Microbiota
  • Micromonospora / chemistry*
  • Phospholipid Transfer Proteins / metabolism
  • Urochordata / microbiology*

Substances

  • Antifungal Agents
  • Benzopyrans
  • Fungal Proteins
  • Isoquinolines
  • Phospholipid Transfer Proteins
  • turbinmicin