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 Märtlbauer; Stephen H. Leppla; Si Ming Man

doi:10.1038/s41467-020-14534-3

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

63 Citations (Scopus)

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 language	English
Article number	760
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-14534-3
Publication status	Published - 1 Dec 2020

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Fox, D., Mathur, A., Xue, Y., Liu, Y., Tan, W. H., Feng, S., Pandey, A., Ngo, C., Hayward, J. A., Atmosukarto, I. I., Price, J. D., Johnson, M. D., Jessberger, N., Robertson, A. A. B., Burgio, G., Tscharke, D. C., Fox, E. M., Leyton, D. L., Kaakoush, N. O., ... Man, S. M. (2020). Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome. Nature Communications, 11(1), Article 760. https://doi.org/10.1038/s41467-020-14534-3

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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 = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

day = "1",

doi = "10.1038/s41467-020-14534-3",

language = "English",

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Fox, D, Mathur, A, Xue, Y, Liu, Y, Tan, WH, Feng, S, Pandey, A, Ngo, C, Hayward, JA, Atmosukarto, II, Price, JD, Johnson, MD, Jessberger, N, Robertson, AAB, Burgio, G , Tscharke, DC, Fox, EM, Leyton, DL, Kaakoush, NO, Märtlbauer, E, Leppla, SH & Man, SM 2020, 'Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome', Nature Communications, vol. 11, no. 1, 760. https://doi.org/10.1038/s41467-020-14534-3

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T1 - Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

AU - Fox, Daniel

AU - Mathur, Anukriti

AU - Xue, Yansong

AU - Liu, Yunqi

AU - Tan, Wei Hong

AU - Feng, Shouya

AU - Pandey, Abhimanu

AU - Ngo, Chinh

AU - Hayward, Jenni A.

AU - Atmosukarto, Ines I.

AU - Price, Jason D.

AU - Johnson, Matthew D.

AU - Jessberger, Nadja

AU - Robertson, Avril A.B.

AU - Burgio, Gaetan

AU - Tscharke, David C.

AU - Fox, Edward M.

AU - Leyton, Denisse L.

AU - Kaakoush, Nadeem O.

AU - Märtlbauer, Erwin

AU - Leppla, Stephen H.

AU - Man, Si Ming

PY - 2020/12/1

Y1 - 2020/12/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-020-14534-3

M3 - Article

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 760

ER -

Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

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