Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway
Enterohemorrhagic <i>Escherichia coli</i> (EHEC) O157:H7 is a foodborne pathogen that causes a variety of diseases, ranging from self-limiting gastroenteritis to life-threatening extra-intestinal diseases such as hemolytic uremic syndrome. EspF, an effector protein secreted by the type I...
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2025-04-01
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| author | Litai Xu Song Liang Yaoguo Wang Min Gao Bao Zhang Wei Zhao Ying Hua Chengsong Wan |
| author_facet | Litai Xu Song Liang Yaoguo Wang Min Gao Bao Zhang Wei Zhao Ying Hua Chengsong Wan |
| author_sort | Litai Xu |
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| description | Enterohemorrhagic <i>Escherichia coli</i> (EHEC) O157:H7 is a foodborne pathogen that causes a variety of diseases, ranging from self-limiting gastroenteritis to life-threatening extra-intestinal diseases such as hemolytic uremic syndrome. EspF, an effector protein secreted by the type III secretion system of EHEC, is primarily responsible for the development of inflammatory colitis. Our previous study revealed that EspF interacts with the host Annexin A6 (ANXA6) protein and targets the endoplasmic reticulum (ER). Given the critical effects of ER stress on the host responses of gastroenteritis, we explored the role of EspF–ANXA6 interaction in ER stress. Caco-2 cells were infected with different strains of EHEC and transfected with modified plasmids to establish in vitro research models. Our results revealed that infection with <i>espF</i>-deletion EHEC strains significantly exacerbated ER stress. Specifically, the phosphorylation of eIF2α was elevated, and the expression levels of BiP, ATF4, and CHOP were increased by more than 15% compared to those in cells infected with wild-type EHEC strains. Further experiments showed that EspF co-localizes with BiP and down-regulates the PERK pathway. Meanwhile, the EspF–ANXA6 interaction could aggravate the inhibition of the PERK pathway and stimulate calcium influx to disturb ER homeostasis, eventually leading to apoptosis. Our findings suggest that the EspF–ANXA6 interaction could inhibit ER stress through the PERK pathway, which may limit cell-to-cell communication and block the clearance of bacteria in host cells. |
| format | Article |
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| institution | DOAJ |
| issn | 2076-0817 |
| language | English |
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| spelling | doaj-art-94ece2e61c9d46d5966a4c0d4779c6dd2025-08-20T03:14:46ZengMDPI AGPathogens2076-08172025-04-0114544010.3390/pathogens14050440Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK PathwayLitai Xu0Song Liang1Yaoguo Wang2Min Gao3Bao Zhang4Wei Zhao5Ying Hua6Chengsong Wan7BSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaDepartment of Laboratory Medicine, Shenzhen Children’s Hospital, Shenzhen 518000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaBSL-3 Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510000, ChinaEnterohemorrhagic <i>Escherichia coli</i> (EHEC) O157:H7 is a foodborne pathogen that causes a variety of diseases, ranging from self-limiting gastroenteritis to life-threatening extra-intestinal diseases such as hemolytic uremic syndrome. EspF, an effector protein secreted by the type III secretion system of EHEC, is primarily responsible for the development of inflammatory colitis. Our previous study revealed that EspF interacts with the host Annexin A6 (ANXA6) protein and targets the endoplasmic reticulum (ER). Given the critical effects of ER stress on the host responses of gastroenteritis, we explored the role of EspF–ANXA6 interaction in ER stress. Caco-2 cells were infected with different strains of EHEC and transfected with modified plasmids to establish in vitro research models. Our results revealed that infection with <i>espF</i>-deletion EHEC strains significantly exacerbated ER stress. Specifically, the phosphorylation of eIF2α was elevated, and the expression levels of BiP, ATF4, and CHOP were increased by more than 15% compared to those in cells infected with wild-type EHEC strains. Further experiments showed that EspF co-localizes with BiP and down-regulates the PERK pathway. Meanwhile, the EspF–ANXA6 interaction could aggravate the inhibition of the PERK pathway and stimulate calcium influx to disturb ER homeostasis, eventually leading to apoptosis. Our findings suggest that the EspF–ANXA6 interaction could inhibit ER stress through the PERK pathway, which may limit cell-to-cell communication and block the clearance of bacteria in host cells.https://www.mdpi.com/2076-0817/14/5/440Enterohemorrhagic <i>Escherichia coli</i>EspF proteinendoplasmic reticulum stressPERK pathway |
| spellingShingle | Litai Xu Song Liang Yaoguo Wang Min Gao Bao Zhang Wei Zhao Ying Hua Chengsong Wan Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway Pathogens Enterohemorrhagic <i>Escherichia coli</i> EspF protein endoplasmic reticulum stress PERK pathway |
| title | Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway |
| title_full | Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway |
| title_fullStr | Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway |
| title_full_unstemmed | Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway |
| title_short | Enterohemorrhagic <i>Escherichia coli</i> O157:H7 Infection Inhibits Host Endoplasmic Reticulum Stress in Intestinal Epithelial Cells via the PERK Pathway |
| title_sort | enterohemorrhagic i escherichia coli i o157 h7 infection inhibits host endoplasmic reticulum stress in intestinal epithelial cells via the perk pathway |
| topic | Enterohemorrhagic <i>Escherichia coli</i> EspF protein endoplasmic reticulum stress PERK pathway |
| url | https://www.mdpi.com/2076-0817/14/5/440 |
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