The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1.
The type III secretion system effector EspO of enterohaemorrhagic Escherichia coli inhibits apoptosis through an interaction with HAX-1.
复制标题
III型分泌系统效应子ESPO肠肠肠肠球菌大肠杆菌通过与HAX-1的相互作用抑制凋亡。
DOI：
10.1111/cmi.13366
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发表时间：
2021-09
影响因子：
3.4
通讯作者：
Clements A
中科院分区：
文献类型：
--
作者：
Chatterjee S;Lekmeechai S;Constantinou N;Grzybowska EA;Kozik Z;Choudhary JS;Berger CN;Frankel G;Clements A
许多肠道病原体利用III型分泌系统(T3SS)将效应蛋白直接转运到宿主细胞的细胞质中，在那里它们颠覆了肠道上皮细胞的信号通路。在这里，我们报道了抗凋亡调节因子HS1相关蛋白X1(HAX-1)是肠出血性大肠杆菌(EHEC)的T3SS效应因子Espo和轮状柠檬酸杆菌、福氏志贺氏菌的Ospe和鼠伤寒沙门氏菌的Osp1STYM的相互作用伙伴。ESPO、OSPE和Osp1STYM与粘着斑蛋白整合素连接激酶(ILK)相互作用。我们发现ESPO既定位于焦点粘连(ILK定位)，也定位于线粒体(HAX-1定位)，并且HAX-1的表达增加导致ESPO的线粒体定位增强。Espo、OSPE和Osp1STYM的异位表达对星形孢菌素和衣霉素诱导的细胞凋亡具有保护作用。耗尽HAX-1细胞表明ESPO的抗细胞凋亡活性依赖于HAX-1。利用T3SS传递的EspO1进一步证实HAX-1和ILK在感染过程中是EspO1相互作用的蛋白。利用细胞脱落作为细胞死亡的指标，我们证实了T3SS介导的EspO1可以抑制EPEC感染过程中诱导的细胞死亡，其程度与抗凋亡效应剂NleH或PAN caspase抑制剂z-VAD处理的程度相似。相反，在缺乏HAX-1的细胞中，EspO1不再能够防止细胞脱离，而NleH1和z-VAD保持其保护活性。因此，在感染和异位表达期间，Espo通过与HAX-1相互作用来保护细胞免于死亡。这些结果表明，尽管EHEC、轮状芽胞杆菌、志贺氏菌和鼠伤寒沙门氏菌感染之间存在差异，劫持HAX-1抗凋亡信号是维持感染细胞活力的常见策略。
Many enteric pathogens employ a type III secretion system (T3SS) to translocate effector proteins directly into the host cell cytoplasm, where they subvert signalling pathways of the intestinal epithelium. Here, we report that the anti-apoptotic regulator HS1-associated protein X1 (HAX-1) is an interaction partner of the T3SS effectors EspO of enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium, OspE of Shigella flexneri and Osp1STYM of Salmonella enterica serovar Typhimurium. EspO, OspE and Osp1STYM have previously been reported to interact with the focal adhesions protein integrin linked kinase (ILK). We found that EspO localizes both to the focal adhesions (ILK localisation) and mitochondria (HAX-1 localisation), and that increased expression of HAX-1 leads to enhanced mitochondrial localisation of EspO. Ectopic expression of EspO, OspE and Osp1STYM protects cells from apoptosis induced by staurosporine and tunicamycin. Depleting cells of HAX-1 indicates that the anti-apoptotic activity of EspO is HAX-1 dependent. Both HAX-1 and ILK were further confirmed as EspO1-interacting proteins during infection using T3SS-delivered EspO1. Using cell detachment as a proxy for cell death we confirmed that T3SS-delivered EspO1 could inhibit cell death induced during EPEC infection, to a similar extent as the anti-apoptotic effector NleH, or treatment with the pan caspase inhibitor z-VAD. In contrast, in cells lacking HAX-1, EspO1 was no longer able to protect against cell detachment, while NleH1 and z-VAD maintained their protective activity. Therefore, during both infection and ectopic expression EspO protects cells from cell death by interacting with HAX-1. These results suggest that despite the differences between EHEC, C. rodentium, Shigella and S. typhimurium infections, hijacking HAX-1 anti-apoptotic signalling is a common strategy to maintain the viability of infected cells.
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影响因子：
3.1
作者：
Günster RA;Matthews SA;Holden DW;Thurston TLM
通讯作者：
Thurston TLM
DOI：
10.1016/j.bbrc.2010.02.084
发表时间：
2010-03-19
影响因子：
3.1
作者：
Kang, Young Ji;Jang, Mi;Park, Sung Goo
通讯作者：
Park, Sung Goo
影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
影响因子：
5.4
作者：
Grzybowska, Ewa A.;Zayat, Valery;Siedlecki, Janusz A.
通讯作者：
Siedlecki, Janusz A.
影响因子：
3.2
作者：
Iguchi, Atsushi;Thomson, Nicholas R.;Frankel, Gad
通讯作者：
Frankel, Gad