TY - JOUR
T1 - The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans
AU - Thevissen, Karin
AU - De Mello Tavares, Patricia
AU - Xu, Deming
AU - Blankenship, Jill
AU - Vandenbosch, Davy
AU - Idkowiak-Baldys, Jolanta
AU - Govaert, Gilmer
AU - Bink, Anna
AU - Rozental, Sonia
AU - De Groot, Piet W.J.
AU - Davis, Talya R.
AU - Kumamoto, Carol A.
AU - Vargas, Gabriele
AU - Nimrichter, Leonardo
AU - Coenye, Tom
AU - Mitchell, Aaron
AU - Roemer, Terry
AU - Hannun, Yusuf A.
AU - Cammue, Bruno P.A.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1365-2958.2012.08017.x
DO - 10.1111/j.1365-2958.2012.08017.x
M3 - Article
C2 - 22384976
AN - SCOPUS:84863396190
SN - 0950-382X
VL - 84
SP - 166
EP - 180
JO - Molecular Microbiology
JF - Molecular Microbiology
IS - 1
ER -