EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases
Enteropathogenic Escherichia coli are bacterial pathogens that colonize the gut and cause severe diarrhea in humans. Upon intimate attachment to the intestinal epithelium, these pathogens translocate via a type III secretion system virulent proteins, termed effectors, into the host cells. These effe...
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Taylor & Francis Group
2022-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2022.2130657 |
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| author | Rachana Pattani Ramachandran Ipsita Nandi Nir Haritan Efrat Zlotkin-Rivkin Yael Keren Tsafi Danieli Mario Lebendiker Naomi Melamed-Book William Breuer Dana Reichmann Benjamin Aroeti |
| author_facet | Rachana Pattani Ramachandran Ipsita Nandi Nir Haritan Efrat Zlotkin-Rivkin Yael Keren Tsafi Danieli Mario Lebendiker Naomi Melamed-Book William Breuer Dana Reichmann Benjamin Aroeti |
| author_sort | Rachana Pattani Ramachandran |
| collection | DOAJ |
| description | Enteropathogenic Escherichia coli are bacterial pathogens that colonize the gut and cause severe diarrhea in humans. Upon intimate attachment to the intestinal epithelium, these pathogens translocate via a type III secretion system virulent proteins, termed effectors, into the host cells. These effectors manipulate diverse host cell organelles and functions for the pathogen’s benefit. However, the precise mechanisms underlying their activities are not fully understood despite intensive research. EspH, a critical effector protein, has been previously reported to disrupt the host cell actin cytoskeleton by suppressing RhoGTPase guanine exchange factors. However, native host proteins targeted by EspH to mediate these activities remained unknown. Here, we identified the active Bcr related (ABR), a protein previously characterized to possess dual Rho guanine nucleotide exchange factor and GTPase activating protein (GAP) domains, as a native EspH interacting partner. These interactions are mediated by the effector protein’s C-terminal 38 amino acid segment. The effector primarily targets the GAP domain of ABR to suppress Rac1 and Cdc42, host cell cytotoxicity, bacterial invasion, and filopodium formation at infection sites. Knockdown of ABR expression abolished the ability of EspH to suppress Rac1, Cdc42. Our studies unravel a novel mechanism by which host RhoGTPases are hijacked by bacterial effectors. |
| format | Article |
| id | doaj-art-cae515c78bef48799a93012d4a88394a |
| institution | OA Journals |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-cae515c78bef48799a93012d4a88394a2025-08-20T02:38:11ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2130657EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPasesRachana Pattani Ramachandran0Ipsita Nandi1Nir Haritan2Efrat Zlotkin-Rivkin3Yael Keren4Tsafi Danieli5Mario Lebendiker6Naomi Melamed-Book7William Breuer8Dana Reichmann9Benjamin Aroeti10Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Protein Production Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Protein Production Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelThe Protein Production Facility, Wolfson Centre for Applied Structural Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelBioimaging Unit, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelProteomics and Mass Spectrometry Unit, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelProteomics and Mass Spectrometry Unit, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Cell and Developmental Biology, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, IsraelEnteropathogenic Escherichia coli are bacterial pathogens that colonize the gut and cause severe diarrhea in humans. Upon intimate attachment to the intestinal epithelium, these pathogens translocate via a type III secretion system virulent proteins, termed effectors, into the host cells. These effectors manipulate diverse host cell organelles and functions for the pathogen’s benefit. However, the precise mechanisms underlying their activities are not fully understood despite intensive research. EspH, a critical effector protein, has been previously reported to disrupt the host cell actin cytoskeleton by suppressing RhoGTPase guanine exchange factors. However, native host proteins targeted by EspH to mediate these activities remained unknown. Here, we identified the active Bcr related (ABR), a protein previously characterized to possess dual Rho guanine nucleotide exchange factor and GTPase activating protein (GAP) domains, as a native EspH interacting partner. These interactions are mediated by the effector protein’s C-terminal 38 amino acid segment. The effector primarily targets the GAP domain of ABR to suppress Rac1 and Cdc42, host cell cytotoxicity, bacterial invasion, and filopodium formation at infection sites. Knockdown of ABR expression abolished the ability of EspH to suppress Rac1, Cdc42. Our studies unravel a novel mechanism by which host RhoGTPases are hijacked by bacterial effectors.https://www.tandfonline.com/doi/10.1080/19490976.2022.2130657Enteropathogenic E. coliType III secreted effectorsEspHRho GTPasesactive Bcr related (ABR)host-pathogen interactions |
| spellingShingle | Rachana Pattani Ramachandran Ipsita Nandi Nir Haritan Efrat Zlotkin-Rivkin Yael Keren Tsafi Danieli Mario Lebendiker Naomi Melamed-Book William Breuer Dana Reichmann Benjamin Aroeti EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases Gut Microbes Enteropathogenic E. coli Type III secreted effectors EspH Rho GTPases active Bcr related (ABR) host-pathogen interactions |
| title | EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases |
| title_full | EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases |
| title_fullStr | EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases |
| title_full_unstemmed | EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases |
| title_short | EspH interacts with the host active Bcr related (ABR) protein to suppress RhoGTPases |
| title_sort | esph interacts with the host active bcr related abr protein to suppress rhogtpases |
| topic | Enteropathogenic E. coli Type III secreted effectors EspH Rho GTPases active Bcr related (ABR) host-pathogen interactions |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2022.2130657 |
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