Sphingolipid biosynthetic pathway is crucial for growth, biofilm formation and membrane integrity of Scedosporium boydii

Future Med Chem. 2019 Nov;11(22):2905-2917. doi: 10.4155/fmc-2019-0186. Epub 2019 Nov 12.

Abstract

Aim: Glycosphingolipids are conserved lipids displaying a variety of functions in fungal cells, such as determination of cell polarity and virulence. They have been considered as potent targets for new antifungal drugs. The present work aimed to test two inhibitors, myriocin and DL-threo-1-Phenyl-2-palmitoylamino-3-morpholino-1-propanol, in Scedosporium boydii, a pathogenic fungus which causes a wide range of disease. Materials & methods: Mass spectrometry, microscopy and cell biology approaches showed that treatment with both inhibitors led to defects in fungal growth and membrane integrity, and caused an increased susceptibility to the current antifungal agents. Conclusion: These data demonstrate the antifungal potential of drugs inhibiting sphingolipid biosynthesis, as well as the usefulness of sphingolipids as promising targets for the development of new therapeutic options.

Keywords: Scedosporium; antifungal drugs; antifungal therapy; biosynthetic pathway; glycosphingolipids; new targets.

Publication types

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

MeSH terms

  • Biofilms / growth & development*
  • Cell Membrane / metabolism
  • Fatty Acids, Monounsaturated / metabolism
  • Meperidine / analogs & derivatives
  • Meperidine / metabolism
  • Scedosporium / metabolism*
  • Sphingolipids / biosynthesis*

Substances

  • Fatty Acids, Monounsaturated
  • Sphingolipids
  • 4-propionyloxy-4-phenyl-N-methylpiperidine
  • Meperidine
  • thermozymocidin