EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases*
Enteropathogenic E. coli (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous ho...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2024.2400575 |
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| author | Ipsita Nandi Rachana Pattani Ramachandran Deborah E. Shalev Dina Schneidman-Duhovny Raisa Shtuhin-Rahav Naomi Melamed-Book Efrat Zlotkin-Rivkin Alexander Rouvinski Ilan Rosenshine Benjamin Aroeti |
| author_facet | Ipsita Nandi Rachana Pattani Ramachandran Deborah E. Shalev Dina Schneidman-Duhovny Raisa Shtuhin-Rahav Naomi Melamed-Book Efrat Zlotkin-Rivkin Alexander Rouvinski Ilan Rosenshine Benjamin Aroeti |
| author_sort | Ipsita Nandi |
| collection | DOAJ |
| description | Enteropathogenic E. coli (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues in EspH. Mutating these sites abolished the ability of EspH to inhibit Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with the Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection. |
| format | Article |
| id | doaj-art-e905527152f04b9a97bcc2fed77a5ebc |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-e905527152f04b9a97bcc2fed77a5ebc2025-08-20T02:16:55ZengTaylor & Francis GroupGut Microbes1949-09761949-09842024-12-0116110.1080/19490976.2024.2400575EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases*Ipsita Nandi0Rachana Pattani Ramachandran1Deborah E. Shalev2Dina Schneidman-Duhovny3Raisa Shtuhin-Rahav4Naomi Melamed-Book5Efrat Zlotkin-Rivkin6Alexander Rouvinski7Ilan Rosenshine8Benjamin Aroeti9Department of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelThe Wolfson Centre for Applied Structural Biology, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelThe Rachel and Selim Benin School of Computer Science and Engineering, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelBioimaging Unit, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, of Jerusalem, Jerusalem, IsraelDepartment of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University-Hadassah Medical School, of Jerusalem, Jerusalem, IsraelDepartment of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, The Edmond J. Safra Campus – Givat Ram, Jerusalem, IsraelEnteropathogenic E. coli (EPEC) is a Gram-negative bacterial pathogen that causes persistent diarrhea. Upon attachment to the apical plasma membrane of the intestinal epithelium, the pathogen translocates virulence proteins called effectors into the infected cells. These effectors hijack numerous host processes for the pathogen’s benefit. Therefore, studying the mechanisms underlying their action is crucial for a better understanding of the disease. We show that translocated EspH interacts with multiple host Rab GTPases. AlphaFold predictions and site-directed mutagenesis identified glutamic acid and lysine at positions 37 and 41 as Rab interacting residues in EspH. Mutating these sites abolished the ability of EspH to inhibit Akt and mTORC1 signaling, lysosomal exocytosis, and bacterial invasion. Knocking out the endogenous Rab8a gene expression highlighted the involvement of Rab8a in Akt/mTORC1 signaling and lysosomal exocytosis. A phosphoinositide binding domain with a critical tyrosine was identified in EspH. Mutating the tyrosine abolished the localization of EspH at infection sites and its capacity to interact with the Rabs. Our data suggest novel EspH-dependent mechanisms that elicit immune signaling and membrane trafficking during EPEC infection.https://www.tandfonline.com/doi/10.1080/19490976.2024.2400575Enteropathogenic e. colitype III secreted effectorsEspHRab GTPasesRho GTPasesphosphoinositides (PIs) |
| spellingShingle | Ipsita Nandi Rachana Pattani Ramachandran Deborah E. Shalev Dina Schneidman-Duhovny Raisa Shtuhin-Rahav Naomi Melamed-Book Efrat Zlotkin-Rivkin Alexander Rouvinski Ilan Rosenshine Benjamin Aroeti EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* Gut Microbes Enteropathogenic e. coli type III secreted effectors EspH Rab GTPases Rho GTPases phosphoinositides (PIs) |
| title | EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* |
| title_full | EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* |
| title_fullStr | EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* |
| title_full_unstemmed | EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* |
| title_short | EspH utilizes phosphoinositide and Rab binding domains to interact with plasma membrane infection sites and Rab GTPases* |
| title_sort | esph utilizes phosphoinositide and rab binding domains to interact with plasma membrane infection sites and rab gtpases |
| topic | Enteropathogenic e. coli type III secreted effectors EspH Rab GTPases Rho GTPases phosphoinositides (PIs) |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2024.2400575 |
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