Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

Daniel Fox, Anukriti Mathur, Yansong Xue, Yunqi Liu, Wei Hong Tan, Shouya Feng, Abhimanu Pandey, Chinh Ngo, Jenni A Hayward, Ines I Atmosukarto, Jason D Price, Matthew D Johnson, Nadja Jessberger, Avril A B Robertson, Gaetan Burgio, David C Tscharke, Edward M Fox, Denisse L Leyton, Nadeem O Kaakoush, Erwin MärtlbauerStephen H Leppla, Si Ming Man

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)
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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.

Original languageEnglish
Article number760
JournalNature Communications
Volume11
Issue number1
Early online date6 Feb 2020
DOIs
Publication statusPublished - 1 Dec 2020

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