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Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B

Kenya E Fernandes1, Richard J Payne2, Dee A Carter3

  • 1School of Life and Environmental Sciences and the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia.

Antimicrobial Agents and Chemotherapy
|July 22, 2020
PubMed

Insights

Lactoferrin peptides significantly boost the antifungal power of amphotericin B. A synthesized peptide, lactofungin, shows superior synergy, offering a promising new antifungal adjuvant.

Area of Science:

  • Biochemistry
  • Mycology
  • Pharmacology

Background:

  • Lactoferrin (LF) possesses broad-spectrum antimicrobial properties.
  • LF synergistically enhances antifungal drug efficacy, particularly with amphotericin B (AMB).
  • Hypothesis: Peptides derived from LF may further augment this synergy.

Purpose of the Study:

  • To investigate if pepsin-derived peptides from LF enhance AMB's antifungal activity.
  • To identify specific peptides responsible for enhanced synergy.
  • To develop a novel peptide-based antifungal adjuvant.

Main Methods:

  • Pepsin digestion of LF under various conditions.
  • Antifungal synergy assays with AMB and LF hydrolysates.
  • Peptide identification using MALDI-TOF mass spectrometry.
  • Virtual peptide digest analysis and sequence prediction.
  • Synthesis and testing of a lead peptide, lactofungin (LFG).

Main Results:

  • LF hydrolysates showed enhanced synergy with AMB compared to intact LF.
  • Fourteen peptides were identified, with sequences predicted.
  • A 30-residue peptide, lactofungin (LFG), was synthesized.
  • Pure LFG demonstrated potent synergy with AMB, surpassing native LF's efficacy across tested fungal species.

Conclusions:

  • Pepsin-derived peptides from LF significantly enhance AMB antifungal activity.
  • LFG is a highly effective antifungal adjuvant with potential for further optimization.
  • LFG represents a promising lead compound for developing novel antifungal therapies.
Keywords:
CandidaCryptococcusamphotericindrug synergylactoferrin

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