title: The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans.
abstract: The antifungal plant defensin RsAFP2 isolated from radish interacts with fungal glucosylceramides and induces apoptosis in Candida albicans. To further unravel the mechanism of RsAFP2 antifungal action and tolerance mechanisms, we screened a library of 2868 heterozygous C. albicans deletion mutants and identified 30 RsAFP2-hypersensitive mutants. The most prominent group of RsAFP2 tolerance genes was involved in cell wall integrity and hyphal growth/septin ring formation. Consistent with these genetic data, we demonstrated that RsAFP2 interacts with the cell wall of C. albicans, which also contains glucosylceramides, and activates the cell wall integrity pathway. Moreover, we found that RsAFP2 induces mislocalization of septins and blocks the yeast-to-hypha transition in C. albicans. Increased ceramide levels have previously been shown to result in apoptosis and septin mislocalization. Therefore, ceramide levels in C. albicans membranes were analysed following RsAFP2 treatment and, as expected, increased accumulation of phytoC24-ceramides in membranes of RsAFP2-treated C. albicans cells was detected. This is the first report on the interaction of a plant defensin with glucosylceramides in the fungal cell wall, causing cell wall stress, and on the effects of a defensin on septin localization and ceramide accumulation.
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), Katholieke Universiteit Leuven, 3001 Heverlee, Belgium. Karin.thevissen@biw.kuleuven.be
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
authors.forename: Patricia
authors.initials: P
authors.lastname: de Mello Tavares
authors.forename: Deming
authors.initials: D
authors.lastname: Xu
authors.forename: Jill
authors.initials: J
authors.lastname: Blankenship
authors.forename: Davy
authors.initials: D
authors.lastname: Vandenbosch
authors.forename: Jolanta
authors.initials: J
authors.lastname: Idkowiak-Baldys
authors.forename: Gilmer
authors.initials: G
authors.lastname: Govaert
authors.forename: Anna
authors.initials: A
authors.lastname: Bink
authors.forename: Sonia
authors.initials: S
authors.lastname: Rozental
authors.forename: Piet W J
authors.initials: PW
authors.lastname: de Groot
authors.forename: Talya R
authors.initials: TR
authors.lastname: Davis
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kumamoto
authors.forename: Gabriele
authors.initials: G
authors.lastname: Vargas
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Tom
authors.initials: T
authors.lastname: Coenye
authors.forename: Aaron
authors.initials: A
authors.lastname: Mitchell
authors.forename: Terry
authors.initials: T
authors.lastname: Roemer
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
mesh_terms: D002176:Candida albicans / Q000254:growth & development* / Q000648:ultrastructure; D002473:Cell Wall / Q000378:metabolism* / Q000648:ultrastructure; D023082:Defensins / Q000378:metabolism*; D005963:Glucosylceramides / Q000378:metabolism*; D025301:Hyphae / Q000254:growth & development; D046529:Microscopy, Electron, Transmission; D010940:Plant Proteins / Q000378:metabolism*; D031224:Raphanus; D058112:Septins / Q000378:metabolism*
chemical_list: D023082:Defensins; D005963:Glucosylceramides; D010940:Plant Proteins; D058112:Septins