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标题：Subtilase cytotoxin from Shiga-toxigenic Escherichia coli impairs the inflammasome and exacerbates enteropathogenic bacterial infection
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作者：Hiroyasu Tsutsuki ; Tianli Zhang ; Kinnosuke Yahiro 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：4
页码：1-25
DOI：10.1016/j.isci.2022.104050
语种：English
出版社：Elsevier
摘要：SummarySubtilase cytotoxin (SubAB) is an AB5toxin mainly produced by the locus of enterocyte effacement-negative Shiga-toxigenicEscherichia coli(STEC) strain such as O113:H21, yet the contribution of SubAB to STEC infectious disease is unclear. We found that SubAB reduced activation of the STEC O113:H21 infection-induced non-canonical NLRP3 inflammasome and interleukin (IL)-1β and IL-18 production in murine macrophages. Downstream of lipopolysaccharide signaling, SubAB suppressed caspase-11 expression by inhibiting interferon-β/STAT1 signaling, followed by disrupting formation of the NLRP3/caspase-1 assembly. These inhibitions were regulated by PERK/IRE1α-dependent endoplasmic reticulum (ER) stress signaling initiated by cleavage of the host ER chaperone BiP by SubAB. Our murine model of SubAB-producingCitrobacter rodentiumdemonstrated that SubAB promotedC. rodentiumproliferation and worsened symptoms such as intestinal hyperplasia and diarrhea. These findings highlight the inhibitory effect of SubAB on the NLRP3 inflammasome via ER stress, which may be associated with STEC survival and infectious disease pathogenicity in hosts.Graphical abstractDisplay OmittedHighlights•SubAB from STEC inhibits inflammasome activation and IL-1β/IL-18 production•SubAB prevents caspase-11 expression via IRE1α/PERK-dependent inhibition of STAT1•SubAB reduces LPS-induced pro-IL-1β production via IRE1α/PERK-dependent pathway•SubAB promotesC. rodentiumsurvival in mouse colon and facilitates the infectionBiochemistry; Protein; Microbiology; Bacteriology