The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans

Karin Thevissen, Patricia De Mello Tavares, Deming Xu, Jill Blankenship, Davy Vandenbosch, Jolanta Idkowiak-Baldys, Gilmer Govaert, Anna Bink, Sonia Rozental, Piet W.J. De Groot, Talya R. Davis, Carol A. Kumamoto, Gabriele Vargas, Leonardo Nimrichter, Tom Coenye, Aaron Mitchell, Terry Roemer, Yusuf A. Hannun, Bruno P.A. Cammue

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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.

Original languageEnglish (US)
Pages (from-to)166-180
Number of pages15
JournalMolecular Microbiology
Volume84
Issue number1
DOIs
StatePublished - Apr 1 2012

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Septins
Defensins
Ceramides
Candida albicans
Cell Wall
Glucosylceramides
Apoptosis
Raphanus
Membranes
Hyphae
Libraries
Yeasts
Growth
Genes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans. / Thevissen, Karin; De Mello Tavares, Patricia; Xu, Deming; Blankenship, Jill; Vandenbosch, Davy; Idkowiak-Baldys, Jolanta; Govaert, Gilmer; Bink, Anna; Rozental, Sonia; De Groot, Piet W.J.; Davis, Talya R.; Kumamoto, Carol A.; Vargas, Gabriele; Nimrichter, Leonardo; Coenye, Tom; Mitchell, Aaron; Roemer, Terry; Hannun, Yusuf A.; Cammue, Bruno P.A.

In: Molecular Microbiology, Vol. 84, No. 1, 01.04.2012, p. 166-180.

Research output: Contribution to journalArticle

Thevissen, K, De Mello Tavares, P, Xu, D, Blankenship, J, Vandenbosch, D, Idkowiak-Baldys, J, Govaert, G, Bink, A, Rozental, S, De Groot, PWJ, Davis, TR, Kumamoto, CA, Vargas, G, Nimrichter, L, Coenye, T, Mitchell, A, Roemer, T, Hannun, YA & Cammue, BPA 2012, 'The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans', Molecular Microbiology, vol. 84, no. 1, pp. 166-180. https://doi.org/10.1111/j.1365-2958.2012.08017.x
Thevissen, Karin ; De Mello Tavares, Patricia ; Xu, Deming ; Blankenship, Jill ; Vandenbosch, Davy ; Idkowiak-Baldys, Jolanta ; Govaert, Gilmer ; Bink, Anna ; Rozental, Sonia ; De Groot, Piet W.J. ; Davis, Talya R. ; Kumamoto, Carol A. ; Vargas, Gabriele ; Nimrichter, Leonardo ; Coenye, Tom ; Mitchell, Aaron ; Roemer, Terry ; Hannun, Yusuf A. ; Cammue, Bruno P.A. / The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans. In: Molecular Microbiology. 2012 ; Vol. 84, No. 1. pp. 166-180.
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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.",
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AU - Blankenship, Jill

AU - Vandenbosch, Davy

AU - Idkowiak-Baldys, Jolanta

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AU - Rozental, Sonia

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AU - Davis, Talya R.

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