Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome.

Autor: Fox D; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Mathur A; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Xue Y; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Liu Y; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Tan WH; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Feng S; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Pandey A; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Ngo C; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Hayward JA; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Atmosukarto II; Lipotek Pty Ltd. The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Price JD; Lipotek Pty Ltd. The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Johnson MD; Research School of Biology, The Australian National University, Canberra, Australia., Jessberger N; Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Oberschleißheim, Germany., Robertson AAB; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, 4072, Australia., Burgio G; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Tscharke DC; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia., Fox EM; Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne, UK., Leyton DL; Research School of Biology, The Australian National University, Canberra, Australia.; Medical School, The Australian National University, Canberra, Australia., Kaakoush NO; School of Medical Sciences, UNSW Sydney, Sydney, NSW, 2052, Australia., Märtlbauer E; Department of Veterinary Sciences, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität München, Oberschleißheim, Germany., Leppla SH; Microbial Pathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Man SM; Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, Australia. siming.man@anu.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2020 Feb 06; Vol. 11 (1), pp. 760. Date of Electronic Publication: 2020 Feb 06.
DOI: 10.1038/s41467-020-14534-3
Abstrakt: 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.
Databáze: MEDLINE