@article{8f2cc76425c34d1a8b8a544c385bd107,
title = "Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome",
abstract = "Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome.",
author = "Daniel Fox and Anukriti Mathur and Yansong Xue and Yunqi Liu and Tan, {Wei Hong} and Shouya Feng and Abhimanu Pandey and Chinh Ngo and Hayward, {Jenni A} and Atmosukarto, {Ines I} and Price, {Jason D} and Johnson, {Matthew D.} and Nadja Jessberger and Robertson, {Avril A B} and Gaetan Burgio and Tscharke, {David C} and Fox, {Edward M} and Leyton, {Denisse L} and Kaakoush, {Nadeem O} and Erwin M{\"a}rtlbauer and Leppla, {Stephen H} and Man, {Si Ming}",
note = "Funding Information: We thank V.M. Dixit (Genentech, USA), K. Schroder (Institute of Molecular Bioscience, Australia), P. Broz (University of Lausanne, Switzerland), J. Mintern (University of Melbourne, Australia), H. Acha-Orbea (University of Lausanne, Switzerland), C. Parish (ANU, Australia), and C. Vinuesa (ANU, Australia) for reagents. We also thank B. Quah (ANU, Australia), C. Gillespie (ANU, Australia), I. Sastalla (National Institutes of Health, USA), M. Rug (Center for Advanced Microscopy, ANU, Australia), and J. Lee (Centre for Advanced Microscopy, ANU, Australia) for assistance. D.F. is supported by an Australian Government Research Training Program (RTP) Scholarship and a John Curtin School of Medical Research Gordon Ada Scholarship. A.M., S.F. and A.P. are supported by a John Curtin School of Medical Research International Ph.D. scholarship. W.H.T. is supported by a Terrell International Undergraduate Scholarship from the Australian National University. G.B. is supported by the National Collaborative Research Infrastructure Strategy (NCRIS) via the Australian Phenomics Network, the National Health and Medical Research Council of Australia under project grant (APP1143008), the Australian Research Council (Discover Project DP180101494) and the National Natural Science Foundation of China (under the project 81772214). D.C.T. is supported by the National Health and Medical Research Council of Australia (under Project Grants APP1084283 and APP1126599 and Senior Research Fellowship APP1104329) and the Australian Research Council (under Discover Project DP190101325). D.L.L. is supported by an Australian Research Council Future Fellowship (FT150100452). N.O.K. is supported by a Career Development Fellowship from the Cancer Institute NSW (15/CDF/1-11) and a UNSW Scientia Fellowship. S.H.L. is supported, in part, by the Intramural Program of the National Institute of Allergy and Infectious Diseases, NIH, USA. S.M. M. is supported by the Australian National University, The Gretel and Gordon Bootes Medical Research Foundation, and the National Health and Medical Research Council of Australia under Project Grants (APP1141504, APP1146864, APP1162103, and APP1163358) and the R.D. Wright Career Development Fellowship (APP1162025). ",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-14534-3",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}