Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1

Kathy Parisi; James A McKenna; Rohan Lowe; Karen S Harris; Thomas Shafee; Rosemary Guarino; Eunice Lee; Nicole L van der Weerden; Mark R Bleackley; Marilyn A Anderson

doi:10.3390/jof10010054

Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1

J Fungi (Basel). 2024 Jan 7;10(1):54. doi: 10.3390/jof10010054.

Authors

Kathy Parisi^{1

2}, James A McKenna^{1

2}, Rohan Lowe^{1

2}, Karen S Harris^{1

2}, Thomas Shafee¹, Rosemary Guarino^{1

2}, Eunice Lee^{1

2}, Nicole L van der Weerden^{1

2}, Mark R Bleackley^{1

2}, Marilyn A Anderson^{1

2}

Affiliations

¹ La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia.
² Hexima Ltd., Preston 3072, Australia.

Abstract

Plant defensins are a large family of small cationic proteins with diverse functions and mechanisms of action, most of which assert antifungal activity against a broad spectrum of fungi. The partial mechanism of action has been resolved for a small number of members of plant defensins, and studies have revealed that many act by more than one mechanism. The plant defensin Ppdef1 has a unique sequence and long loop 5 with fungicidal activity against a range of human fungal pathogens, but little is known about its mechanism of action. We screened the S. cerevisiae non-essential gene deletion library and identified the involvement of the mitochondria in the mechanism of action of Ppdef1. Further analysis revealed that the hyperpolarisation of the mitochondrial membrane potential (MMP) activates ROS production, vacuolar fusion and cell death and is an important step in the mechanism of action of Ppdef1, and it is likely that a similar mechanism acts in Trichophyton rubrum.

Keywords: Ppdef1; S. cerevisiae; Trichophyton rubrum; antifungal; hyperpolarisation; plant defensin.

Grants and funding

This research received no external funding. In addition to their roles at La Trobe University, K.P., N.L.v.d.W., J.A.M., R.L., R.G., E.L., K.S.H., M.R.B. and M.A.A. were employees of Hexima Ltd. Hexima Ltd. funded the research described in this manuscript.