Calcium homeostasis plays important roles in the internalisation and activities of the small synthetic antifungal peptide PAF26

Alexander, A. J.T. , Muñoz, A., Marcos, J. F. and Read, N. D. (2020) Calcium homeostasis plays important roles in the internalisation and activities of the small synthetic antifungal peptide PAF26. Molecular Microbiology, 114(4), pp. 521-535. (doi: 10.1111/mmi.14532)

Abstract

Fungal diseases are responsible for the deaths of over 1.5 million people worldwide annually. Antifungal peptides represent a useful source of antifungals with novel mechanisms-of-action, and potentially provide new methods of overcoming resistance. Here we investigate the mode-of-action of the small, rationally designed synthetic antifungal peptide PAF26 using the model fungus Neurospora crassa. Here we show that the cell killing activity of PAF26 is dependent on extracellular Ca2+ and the presence of fully functioning fungal Ca2+ homeostatic/signalling machinery. In a screen of mutants with deletions in Ca2+-signalling machinery, we identified three mutants more tolerant to PAF26. The Ca2+ ATPase NCA-2 was found to be involved in the initial interaction of PAF26 with the cell envelope. The vacuolar Ca2+ channel YVC-1 was shown to be essential for its accumulation and concentration within the vacuolar system. The Ca2+ channel CCH-1 was found to be required to prevent the translocation of PAF26 across the plasma membrane. In the wild type, Ca2+ removal from the medium resulted in the peptide remaining trapped in small vesicles as in the Δyvc-1 mutant. It is therefore apparent that cell killing by PAF26 is complex and unusually dependent on extracellular Ca2+ and components of the Ca2+-regulatory machinery.

• Item Type: Articles
• Additional Information: Funding for this project was provided by a Biotechnology and Biological Sciences Research Council Research Studentship to AJTA.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Alexander, Dr Akira
• Authors: Alexander, A. J.T., Muñoz, A., Marcos, J. F., and Read, N. D.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Molecular Microbiology
• Publisher: Wiley
• ISSN: 0950-382X
• ISSN (Online): 1365-2958
• Published Online: 17 June 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Molecular Microbiology 114(4): 521-535
• Publisher Policy: Reproduced under a Creative Commons licence
• Data DOI: 10.17632/sb2r2zsxdz.1