The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity
Enteropathogenic E. coli (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic atta...
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2483777 |
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| author | Akila U. Pilapitiya Lilian Hor Jing Pan Lakshmi C. Wijeyewickrema Robert N. Pike Denisse L. Leyton Jason J Paxman Begoña Heras |
| author_facet | Akila U. Pilapitiya Lilian Hor Jing Pan Lakshmi C. Wijeyewickrema Robert N. Pike Denisse L. Leyton Jason J Paxman Begoña Heras |
| author_sort | Akila U. Pilapitiya |
| collection | DOAJ |
| description | Enteropathogenic E. coli (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic attaching and effacing lesions on the intestinal epithelium. In this study, we present the crystal structure of the EspC passenger domain (αEspC) revealing a toxin comprised a serine protease attached to a large β-helix with additional subdomains. Using various modified EspC expression constructs, alongside type III secretion system-mediated cell internalization assays, we dissect how the αEspC structural features enable toxin entry into the intestinal epithelium to cause cell cytotoxicity. |
| format | Article |
| id | doaj-art-eac669355b7e4482815267027ffa8b01 |
| institution | DOAJ |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Gut Microbes |
| spelling | doaj-art-eac669355b7e4482815267027ffa8b012025-08-20T02:53:44ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2483777The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicityAkila U. Pilapitiya0Lilian Hor1Jing Pan2Lakshmi C. Wijeyewickrema3Robert N. Pike4Denisse L. Leyton5Jason J Paxman6Begoña Heras7Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaResearch School of Biology, Australian National University, Canberra, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaDepartment of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, School of Agriculture, Biomedicine and Environment, La Trobe University, Bundoora, AustraliaEnteropathogenic E. coli (EPEC) is a significant cause of diarrhea, leading to high infant mortality rates. A key toxin produced by EPEC is the EspC autotransporter, which is regulated alongside genes from the locus of enterocyte effacement (LEE), which collectively result in the characteristic attaching and effacing lesions on the intestinal epithelium. In this study, we present the crystal structure of the EspC passenger domain (αEspC) revealing a toxin comprised a serine protease attached to a large β-helix with additional subdomains. Using various modified EspC expression constructs, alongside type III secretion system-mediated cell internalization assays, we dissect how the αEspC structural features enable toxin entry into the intestinal epithelium to cause cell cytotoxicity.https://www.tandfonline.com/doi/10.1080/19490976.2025.2483777Enteropathogenic E. coliautotransporter proteinserine proteasetoxinsbacterial infectionssecretion system |
| spellingShingle | Akila U. Pilapitiya Lilian Hor Jing Pan Lakshmi C. Wijeyewickrema Robert N. Pike Denisse L. Leyton Jason J Paxman Begoña Heras The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity Gut Microbes Enteropathogenic E. coli autotransporter protein serine protease toxins bacterial infections secretion system |
| title | The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| title_full | The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| title_fullStr | The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| title_full_unstemmed | The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| title_short | The crystal structure of the toxin EspC from enteropathogenic Escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| title_sort | crystal structure of the toxin espc from enteropathogenic escherichia coli reveals the mechanism that governs host cell entry and cytotoxicity |
| topic | Enteropathogenic E. coli autotransporter protein serine protease toxins bacterial infections secretion system |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2483777 |
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