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Invasive fungi-derived defensins kill drug-resistant bacterial pathogens

Jiajia Wu1, Shijie Liu1, Hao Wang1

  • 1Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao, Zhongguancun, Beijing 100190, China.

Peptides
|November 28, 2017
PubMed

Insights

Researchers discovered 68 new fungal defensin-like peptides (fDLPs), including a potent synthetic defensin, scedosporisin. This compound effectively combats resistant bacteria like MRSA and VRE with low toxicity, offering a promising new avenue for antimicrobial drug development.

Area of Science:

  • Microbiology
  • Biochemistry
  • Drug Discovery

Background:

  • Fungi-derived defensins are antimicrobial peptides with therapeutic potential.
  • Genomic strategies enable the discovery of novel antimicrobial compounds.

Purpose of the Study:

  • To identify and characterize new fungal defensin-like peptides (fDLPs).
  • To evaluate the therapeutic potential of a novel synthetic defensin, scedosporisin, against resistant bacteria.

Main Methods:

  • Genomic identification of 68 fDLPs across five fungal genera.
  • Characterization of synthetic scedosporisin, including antibacterial activity, toxicity, and stability assays.
  • In vivo efficacy testing in a murine peritonitis model.
  • Homology modeling for structural analysis.

Main Results:

  • Identified 68 fDLPs in five new genera.
  • Scedosporisin demonstrated potent activity against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE).
  • Scedosporisin exhibited low cytotoxicity, low hemolysis, high serum stability, and superior killing kinetics compared to vancomycin against MRSA.
  • In vivo studies showed improved survival rates in mice.

Conclusions:

  • The study significantly expanded the library of fungal defensin-like peptides.
  • Scedosporisin represents a promising lead candidate for developing new antimicrobial agents against resistant bacterial infections.
Keywords:
FungiHydrophobicityScedosporiumVancomycin-resistant Enterococci

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