Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival.
Subtilase cytotoxin induces a novel form of Lipocalin 2, which promotes Shiga-toxigenic Escherichia coli survival.
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枯草酶细胞毒素诱导一种新形式的脂钙蛋白2，促进志贺毒素大肠杆菌的存活。
DOI：
10.1038/s41598-020-76027-z
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发表时间：
2020-11-03
影响因子：
4.6
通讯作者：
Moss J
中科院分区：
文献类型：
--
作者：
Yahiro K;Ogura K;Goto Y;Iyoda S;Kobayashi T;Takeuchi H;Ohnishi M;Moss J
产志贺毒素大肠杆菌（STEC）感染会导致严重的血性腹泻、肾衰竭和溶血性尿毒症综合征。近期研究表明，肠细胞脱落位点（LEE）阴性的STEC感染在全球范围内呈上升趋势。一些LEE阴性的STEC会产生枯草杆菌蛋白酶细胞毒素（SubAB），它能切割内质网（ER）伴侣蛋白BiP，诱导内质网应激和细胞凋亡。在本研究中，我们报道SubAB可诱导一种新型脂质运载蛋白 - 2（LCN2）的表达，并描述其生物学活性以及对细胞凋亡的影响。SubAB诱导了一种新型LCN2的表达，其受双链RNA依赖的蛋白激酶R样内质网激酶通过C/EBP同源蛋白通路调控。SubAB诱导的新型LCN2未分泌到培养上清液中。通过添加全转铁蛋白或氯化铁提高细胞内铁水平可抑制SubAB诱导的多聚ADP - 核糖聚合酶（PARP）切割。正常大小的带FLAG标签的LCN2可抑制STEC生长，但在SubAB或衣霉素诱导的未糖基化的带FLAG标签的LCN2存在时，这种抑制作用未出现。我们的研究表明，SubAB诱导的新型LCN2不具有抗STEC活性，这表明SubAB在LEE阴性STEC的存活以及诱导宿主细胞凋亡方面起着至关重要的作用。
Shiga-toxigenic Escherichia coli (STEC) infection causes severe bloody diarrhea, renal failure, and hemolytic uremic syndrome. Recent studies showed global increases in Locus for Enterocyte Effacement (LEE)-negative STEC infection. Some LEE-negative STEC produce Subtilase cytotoxin (SubAB), which cleaves endoplasmic reticulum (ER) chaperone protein BiP, inducing ER stress and apoptotic cell death. In this study, we report that SubAB induces expression of a novel form of Lipocalin-2 (LCN2), and describe its biological activity and effects on apoptotic cell death. SubAB induced expression of a novel LCN2, which was regulated by PRKR-like endoplasmic reticulum kinase via the C/EBP homologous protein pathway. SubAB-induced novel-sized LCN2 was not secreted into the culture supernatant. Increased intracellular iron level by addition of holo-transferrin or FeCl3 suppressed SubAB-induced PARP cleavage. Normal-sized FLAG-tagged LCN2 suppressed STEC growth, but this effect was not seen in the presence of SubAB- or tunicamycin-induced unglycosylated FLAG-tagged LCN2. Our study demonstrates that SubAB-induced novel-sized LCN2 does not have anti-STEC activity, suggesting that SubAB plays a crucial role in the survival of LEE-negative STEC as well as inducing apoptosis of the host cells.
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影响因子：
5.7
作者：
Kim SL;Lee ST;Min IS;Park YR;Lee JH;Kim DG;Kim SW
通讯作者：
Kim SW
影响因子：
6
作者：
Bu, De-xiu;Hemdahl, Anne-Louise;Yan, Zhong-qun
通讯作者：
Yan, Zhong-qun
DOI：
10.1073/pnas.0510847103
发表时间：
2006-02-07
影响因子：
11.1
作者：
Berger, T;Togawa, A;Mak, TW
通讯作者：
Mak, TW
影响因子：
16
作者：
Goetz, DH;Holmes, MA;Strong, RK
通讯作者：
Strong, RK
影响因子：
3.7
作者：
Cole JN;Nizet V
通讯作者：
Nizet V