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1423486_van der Weerden,N_2023.pdf (3.51 MB)

The Plant Defensin Ppdef1 Is a Novel Topical Treatment for Onychomycosis

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posted on 2023-12-01, 02:18 authored by Nicole Van Der WeerdenNicole Van Der Weerden, Kathy ParisiKathy Parisi, James McKennaJames McKenna, Brigitte Hayes, Peta J Harvey, Pedro Quimbar Dominguez, Sean R Wevrett, Prem Veneer, Owen McCorkelle, Shaily Vasa, Rosemary Guarino, Simon Poon, Yolanda Gaspar, Michael J Baker, David J Craik, Rob B Turner, Marc B Brown, Mark BleackleyMark Bleackley, Marilyn AndersonMarilyn Anderson
Onychomycosis, or fungal nail infection, causes not only pain and discomfort but can also have psychological and social consequences for the patient. Treatment of onychomycosis is complicated by the location of the infection under the nail plate, meaning that antifungal molecules must either penetrate the nail or be applied systemically. Currently, available treatments are limited by their poor nail penetration for topical products or their potential toxicity for systemic products. Plant defensins with potent antifungal activity have the potential to be safe and effective treatments for fungal infections in humans. The cystine-stabilized structure of plant defensins makes them stable to the extremes of pH and temperature as well as digestion by proteases. Here, we describe a novel plant defensin, Ppdef1, as a peptide for the treatment of fungal nail infections. Ppdef1 has potent, fungicidal activity against a range of human fungal pathogens, including Candida spp., Cryptococcus spp., dermatophytes, and non-dermatophytic moulds. In particular, Ppdef1 has excellent activity against dermatophytes that infect skin and nails, including the major etiological agent of onychomycosis Trichophyton rubrum. Ppdef1 also penetrates human nails rapidly and efficiently, making it an excellent candidate for a novel topical treatment of onychomycosis.

Funding

In addition to their roles at La Trobe University, N.L.v.d.W., K.P., B.M.H., J.A.M., Y.M.G., M.J.B., P.Q., S.P., P.K.V., M.J.B., O.M., S.V., R.G., M.R.B. and M.A.A. were employees of Hexima Ltd. Hexima funded the research described in this manuscript. Work in DJCs lab on peptide structures is supported by the access to the facilities of the ARC Centre of Excellence for Innovations in Peptide and Protein Science (CE200100012) and by an Australian Research Council Laureate Fellowship (FL150100146).

History

Publication Date

2023-11-17

Journal

Journal of Fungi

Volume

9

Issue

11

Article Number

1111

Pagination

16p.

Publisher

MDPI

ISSN

2309-608X

Rights Statement

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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