EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation

JS Pearson; C Giogha; S Mühlen; U Nachbur; CLL Pham; Y Zhang; JM Hildebrand; CV Oates; TWF Lung; D Ingle; LF Dagley; A Bankovacki; EJ Petrie; GN Schroeder; VF Crepin; G Frankel; SL Masters; J Vince; JM Murphy; M Sunde; AI Webb; J Silke; EL Hartland

Journal article

EspL is a bacterial cysteine protease effector that cleaves RHIM proteins to block necroptosis and inflammation

JS Pearson, C Giogha, S Mühlen, U Nachbur, CLL Pham, Y Zhang, JM Hildebrand, CV Oates, TWF Lung, D Ingle, LF Dagley, A Bankovacki, EJ Petrie, GN Schroeder, VF Crepin, G Frankel, SL Masters, J Vince, JM Murphy, M Sunde Show all

Nature Microbiology | NATURE PUBLISHING GROUP | Published : 2017

DOI: 10.1038/nmicrobiol.2016.258

Abstract

Cell death signalling pathways contribute to tissue homeostasis and provide innate protection from infection. Adaptor proteins such as receptor-interacting serine/threonine-protein kinase 1 (RIPK1), receptor-interacting serine/threonine-protein kinase 3 (RIPK3), TIR-domain-containing adapter-inducing interferon-β (TRIF) and Z-DNA-binding protein 1 (ZBP1)/DNA-dependent activator of IFN-regulatory factors (DAI) that contain receptor-interacting protein (RIP) homotypic interaction motifs (RHIM) play a key role in cell death and inflammatory signalling 1-3. RHIM-dependent interactions help drive a caspase-independent form of cell death termed necroptosis 4,5. Here, we report that the bacterial p..

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University of Melbourne Researchers

Cristina Giogha Author

Ulrich Nachbur Author

Ying Zhang Author

Joanne Hildebrand Author

Grants

Awarded by University of Melbourne

Funding Acknowledgements

The authors thank E. Mocarski (Emory University) for the gift of Flag-ZBP1/DAI and Flag-M45 and G. Belz (Walter and Eliza Hall Institute) for animal ethics assistance. The authors thank S. Young (Walter and Eliza Hall Institute) for technical assistance. This work was supported by the Australian National Health and Medical Research Council (program grant ID606788 to E.L.H., project grants APP1057888 to J.S., APP1051210 to J.V. and APP1057905 to J.M.M. and J.S., fellowships APP1090108 to J.S.P., APP1052598 to J.V. and APP1105754 to J.M.M.) and the Australian Research Council (Future Fellowship FT130100166 to U.N., Discovery Project DP150104227 to M.S.). C.G. and D.I. were supported by Australian Postgraduate Awards. T.W.F.K. was supported by a University of Melbourne International Research Scholarship (MIRS). G.N.S. is funded by the Medical Research Council, UK. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS.