Abstract
Enterohemorrhagic E. coli (EHEC) is a highly pathogenic bacterial strain capable of inducing severe gastrointestinal disease. Here, we show that EHEC uses the T3SS effector NleF to counteract the host inflammatory response by dampening caspase-4-mediated inflammatory epithelial cell death and by preventing the production of IL-1β. The other two inflammatory caspases, caspase-1 and caspase-5, are not involved in EHEC ΔnleF-induced inflammatory cell death. We found that NleF not only interrupted the heterodimerization of caspase-4-p19 and caspase-4-p10, but also inhibited the interaction of caspase-1 and caspase-4. The last four amino acids of the NleF carboxy terminus are essential in inhibiting caspase-4-dependent inflammatory cell death.
MeSH terms
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Caspases, Initiator / genetics
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Caspases, Initiator / metabolism*
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Cell Line, Tumor
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Enteropathogenic Escherichia coli / genetics
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Enteropathogenic Escherichia coli / metabolism*
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Enteropathogenic Escherichia coli / pathogenicity
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Epithelial Cells / metabolism*
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Epithelial Cells / pathology
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism*
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Humans
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Inflammation / genetics
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Inflammation / metabolism
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Inflammation / microbiology
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Protein Domains
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Virulence Factors / genetics
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Virulence Factors / metabolism*
Substances
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Escherichia coli Proteins
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IL1B protein, human
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Interleukin-1beta
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NleF protein, E coli
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Virulence Factors
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CASP4 protein, human
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Caspases, Initiator