Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

Fox, Daniel, Mathur, Anukriti, Xue, Yansong, Liu, Yunqi, Tan, Wei Hong, Feng, Shouya, Pandey, Abhimanu, Ngo, Chinh, Hayward, Jenni A., Atmosukarto, Ines I., Price, Jason D., Johnson, Matthew D., Jessberger, Nadja, Robertson, Avril A. B., Burgio, Gaetan, Tscharke, David C., Fox, Edward M., Leyton, Denisse L., Kaakoush, Nadeem O., Märtlbauer, Erwin, Leppla, Stephen H. and Man, Si Ming (2020) Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome. Nature Communications, 11 (1). p. 760. ISSN 2041-1723

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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.

Item Type: Article
Subjects: C400 Genetics
C700 Molecular Biology, Biophysics and Biochemistry
F100 Chemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Elena Carlaw
Date Deposited: 27 Feb 2020 16:38
Last Modified: 31 Jul 2021 19:34

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