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 Bruijn, Kevin MacKenzie, Ariane Willems, Aleksandra Toloczko, Javier Diéguez-Uribeondo, Tim Rasmussen, Thomas Schrader, Peter Bayer, Chris J. Secombes and Pieter West ()
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Franziska Trusch: University of Aberdeen
Lars Loebach: University of Aberdeen
Stephan Wawra: University of Aberdeen
Elaine Durward: University of Aberdeen
Andreas Wuensch: University of Aberdeen
Nurul Aqilah Iberahim: University of Aberdeen
Irene Bruijn: University of Aberdeen
Kevin MacKenzie: University of Aberdeen
Ariane Willems: University of Aberdeen
Aleksandra Toloczko: University of Aberdeen
Javier Diéguez-Uribeondo: Real Jardín Botánico CSIC
Tim Rasmussen: University of Aberdeen
Thomas Schrader: University of Duisburg-Essen
Peter Bayer: University of Duisburg-Essen
Chris J. Secombes: University of Aberdeen
Pieter West: University of Aberdeen

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04796-3

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