Cell entry of a host targeting protein of oomycetes requires gp96

Franziska Trusch, Lars Loebach, Stephan Wawra, Elaine Durward, Andreas Wuensch, Nurul Aqilah Iberahim, Irene De Bruijn, Kevin Scott MacKenzie, Ariane Willems, Aleksandra Toloczko-Grabarek, Javier Dieguez-Uribeondo, Tim Rasmussen, Thomas Schrader, Peter Bayer, Christopher John Secombes, Pieter Van West

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Abstract

The animal-pathogenic oomycete Saprolegnia parasitica causes serious losses in aquaculture by infecting and killing freshwater fish. Like plant-pathogenic oomycetes, S. parasitica employs similar infection structures and secretes effector proteins that translocate into host cells to manipulate the host. Here, we show that the host-targeting protein SpHtp3 enters fish cells in a pathogen-independent manner. This uptake process is guided by a gp96-like receptor and can be inhibited by supramolecular tweezers. The C-terminus of SpHtp3 (containing the amino acid sequence YKARK), and not the N-terminal RxLR motif, is responsible for the uptake into host cells. Following translocation, SpHtp3 is released from vesicles into the cytoplasm by another host-targeting protein where it degrades nucleic acids. The effector translocation mechanism described here, is potentially also relevant for other pathogen–host interactions as gp96 is found in both animals and plants.
Original languageEnglish
Article number2347
Pages (from-to)1-12
Number of pages12
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 14 Jun 2018

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    Trusch, F., Loebach, L., Wawra, S., Durward, E., Wuensch, A., Iberahim, N. A., De Bruijn, I., MacKenzie, K. S., Willems, A., Toloczko-Grabarek, A., Dieguez-Uribeondo, J., Rasmussen, T., Schrader, T., Bayer, P., Secombes, C. J., & Van West, P. (2018). Cell entry of a host targeting protein of oomycetes requires gp96. Nature Communications, 9, 1-12. [2347]. https://doi.org/10.1038/s41467-018-04796-3