Subtilase cytotoxin from Shiga-toxigenic Escherichia coli impairs the inflammasome and exacerbates enteropathogenic bacterial infection.
Subtilase cytotoxin from Shiga-toxigenic Escherichia coli impairs the inflammasome and exacerbates enteropathogenic bacterial infection.
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DOI：
10.1016/j.isci.2022.104050
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发表时间：
2022-04-15
期刊：
影响因子：
5.8
通讯作者：
Sawa T
中科院分区：
文献类型：
--
作者：
Tsutsuki H;Zhang T;Yahiro K;Ono K;Fujiwara Y;Iyoda S;Wei FY;Monde K;Seto K;Ohnishi M;Oshiumi H;Akaike T;Sawa T
志贺毒素细胞毒素（SubAB）是一种主要由肠细胞脱落位点阴性的产志贺毒素大肠杆菌（STEC）菌株（如O113:H21）产生的AB5毒素，但SubAB对STEC感染性疾病的作用尚不清楚。我们发现SubAB降低了STEC O113:H21感染诱导的非经典NLRP3炎症小体的活化以及小鼠巨噬细胞中白细胞介素（IL）-1β和IL - 18的产生。在脂多糖信号传导的下游，SubAB通过抑制干扰素-β/STAT1信号传导来抑制caspase - 11的表达，进而破坏NLRP3/caspase - 1复合物的形成。这些抑制作用是由SubAB切割宿主内质网伴侣蛋白BiP所引发的依赖于PERK/IRE1α的内质网（ER）应激信号传导所调节的。我们的产SubAB的啮齿柠檬酸杆菌小鼠模型表明，SubAB促进了啮齿柠檬酸杆菌的增殖，并加重了肠道增生和腹泻等症状。这些发现强调了SubAB通过内质网应激对NLRP3炎症小体的抑制作用，这可能与STEC在宿主中的存活以及感染性疾病的致病性有关。
产志贺毒素大肠杆菌的SubAB抑制炎症小体活化和IL - 1β/IL - 18的产生
SubAB通过依赖IRE1α/PERK对STAT1的抑制来阻止caspase - 11的表达
SubAB通过依赖IRE1α/PERK的途径减少脂多糖诱导的前体IL - 1β的产生
SubAB促进啮齿柠檬酸杆菌在小鼠结肠中的存活并促进感染
生物化学；蛋白质；微生物学；细菌学
Subtilase cytotoxin (SubAB) is an AB5 toxin mainly produced by the locus of enterocyte effacement-negative Shiga-toxigenic Escherichia 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-producing Citrobacter rodentium demonstrated that SubAB promoted C. rodentium proliferation 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. 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 promotes C. rodentium survival in mouse colon and facilitates the infection Biochemistry; Protein; Microbiology; Bacteriology
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枯草酶细胞毒素诱导一种新型的脂肪蛋白2，从而促进shiga-toxigenic escherichia coli大肠杆菌存活。
影响因子：
4.6
作者：
Yahiro K;Ogura K;Goto Y;Iyoda S;Kobayashi T;Takeuchi H;Ohnishi M;Moss J
通讯作者：
Moss J
影响因子：
32.4
作者：
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通讯作者：
O'Riordan MX
影响因子：
5.2
作者：
Fierz L;Cernela N;Hauser E;Nüesch-Inderbinen M;Stephan R
通讯作者：
Stephan R
影响因子：
4.8
作者：
Gunduz F;Aboulnasr FM;Chandra PK;Hazari S;Poat B;Baker DP;Balart LA;Dash S
通讯作者：
Dash S
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J