{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:52:58Z","timestamp":1772160778651,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    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\u2010of\u2010action, and potentially provide new methods of overcoming resistance. Here we investigate the mode\u2010of\u2010action of the small, rationally designed synthetic antifungal peptide PAF26 using the model fungus\n                    <jats:italic>Neurospora crassa<\/jats:italic>\n                    . Here we show that the cell killing activity of PAF26 is dependent on extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and the presence of fully functioning fungal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostatic\/signaling machinery. In a screen of mutants with deletions in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010signaling machinery, we identified three mutants more tolerant to PAF26. The Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ATPase NCA\u20102 was found to be involved in the initial interaction of PAF26 with the cell envelope. The vacuolar Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel YVC\u20101 was shown to be essential for its accumulation and concentration within the vacuolar system. The Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel CCH\u20101 was found to be required to prevent the translocation of PAF26 across the plasma membrane. In the wild type, Ca\n                    <jats:sup>2+<\/jats:sup>\n                    removal from the medium resulted in the peptide remaining trapped in small vesicles as in the\n                    <jats:italic>\u0394yvc\u20101<\/jats:italic>\n                    mutant. It is, therefore, apparent that cell killing by PAF26 is complex and unusually dependent on extracellular Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and components of the Ca\n                    <jats:sup>2+<\/jats:sup>\n                    \u2010regulatory machinery.\n                  <\/jats:p>","DOI":"10.1111\/mmi.14532","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T18:00:37Z","timestamp":1592416837000},"page":"521-535","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Calcium homeostasis plays important roles in the internalization and activities of the small synthetic antifungal peptide PAF26"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1601-619X","authenticated-orcid":false,"given":"Akira J. 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