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Chemistry; Biosynthesis

Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B

Kenya E. Fernandes, Richard J. Payne, Dee A. Carter
Kenya E. Fernandes
aSchool of Life and Environmental Sciences and the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia
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Richard J. Payne
bSchool of Chemistry, University of Sydney, Sydney, NSW, Australia
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Dee A. Carter
aSchool of Life and Environmental Sciences and the Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia
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DOI: 10.1128/AAC.00842-20
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ABSTRACT

Lactoferrin (LF) is an iron-binding glycoprotein with broad-spectrum antimicrobial activity. Previously, we discovered that LF synergistically enhanced the antifungal efficacy of amphotericin B (AMB) across a variety of yeast species and subsequently hypothesized that this synergy was enhanced by the presence of small peptides derived from the whole LF molecule. In this study, LF was digested with pepsin under a range of conditions. The resulting hydrolysates exhibited enhanced synergy with AMB compared to its synergy with undigested LF. Samples were analyzed using matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry, and 14 peptides were identified. The sequences of these peptides were predicted by matching their molecular weights to those of a virtual digest with pepsin. The relative intensities of predicted peptides in each hydrolysate were compared with the activity of the hydrolysate, and the structural and physicochemical properties of the peptides were assessed. From this, a 30-residue peptide was selected for synthesis and dubbed lactofungin (LFG). Pure LFG was highly synergistic with AMB, outperforming native LF in all fungal species tested. With potential for further structural and chemical improvements, LFG is an excellent lead for development as an antifungal adjuvant.

FOOTNOTES

    • Received 5 May 2020.
    • Returned for modification 22 June 2020.
    • Accepted 11 July 2020.
    • Accepted manuscript posted online 20 July 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

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Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B
Kenya E. Fernandes, Richard J. Payne, Dee A. Carter
Antimicrobial Agents and Chemotherapy Sep 2020, 64 (10) e00842-20; DOI: 10.1128/AAC.00842-20

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Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin B
Kenya E. Fernandes, Richard J. Payne, Dee A. Carter
Antimicrobial Agents and Chemotherapy Sep 2020, 64 (10) e00842-20; DOI: 10.1128/AAC.00842-20
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KEYWORDS

Candida
Cryptococcus
amphotericin
drug synergy
lactoferrin

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