title: Antifungal peptides: To be or not to be membrane active.
abstract: Most antifungal peptides (AFPs), if not all, have membrane activity, while some also have alternative targets. Fungal membranes share many characteristics with mammalian membranes with only a few differences, such as differences in sphingolipids, phosphatidylinositol (PI) content and the main sterol is ergosterol. Fungal membranes are also more negative and a better target for cationic AFPs. Targeting just the fungal membrane lipids such as phosphatidylinositol and/or ergosterol by AFPs often translates into mammalian cell toxicity. Conversely, a specific AFP target in the fungal pathogen, such as glucosylceramide, mannosyldiinositol phosphorylceramide or a fungal protein target translates into high pathogen selectivity. However, a lower target concentration, absence or change in the specific fungal target can naturally lead to resistance, although such resistance in turn could result in reduced pathogen virulence. The question is then to be or not to be membrane active - what is the best choice for a successful AFP? In this review we deliberate on this question by focusing on the recent advances in our knowledge on how natural AFPs target fungi.
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, South Africa. Electronic address: mra@sun.ac.za.
authors.forename: Marina
authors.initials: M
authors.lastname: Rautenbach
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, South Africa.
authors.forename: Anscha M
authors.initials: AM
authors.lastname: Troskie
authors.affiliation: BIOPEP Peptide Group, Department of Biochemistry, University of Stellenbosch, South Africa.
authors.forename: J Arnold
authors.initials: JA
authors.lastname: Vosloo
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002473:Cell Wall / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D005658:Fungi / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D047071:beta-Glucans / Q000737:chemistry / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D008563:Membrane Lipids; D010455:Peptides; D047071:beta-Glucans
keywords: Antifungal peptides; Cell membrane; Cell wall; Membrane lipids; Mode of action