Research ArticleCELL DEATH

Shiga toxin suppresses noncanonical inflammasome responses to cytosolic LPS

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Science Immunology  27 Nov 2020:
Vol. 5, Issue 53, eabc0217
DOI: 10.1126/sciimmunol.abc0217

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Paring down pyroptosis

Shiga toxin is a phage-encoded exotoxin that interrupts protein translation and functions as a virulence factor for enterohemorrhagic Escherichia coli (EHEC), a human pathogen causing hemorrhagic colitis and acute renal failure. Havira et al. screened a panel of EHEC mutants lacking various virulence factors for mutants that interfered with inflammasome-mediated cell death. EHEC strains lacking Shiga toxin were more potent inducers of macrophage pyroptosis and IL-1β secretion than wild-type EHEC. Shiga toxin from wild-type EHEC interfered with pyroptosis by blocking the ability of the activated form of caspase-11, a cytoplasmic LPS sensor, to cleave gasdermin D and initiate formation of gasdermin pores in the plasma membrane. This unanticipated activity of Shiga toxin provides EHEC with an additional means of evading the innate immune system.

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