Dual roles of host N-glycosylation in enteropathogenic Escherichia coli infection
8 affiliations
- 1Department of Microbiology and Molecular Genetics, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
- 2Hadassah Organoid Center, The Hadassah Medical Organization, Jerusalem 9166100, Israel
- 3Department of Pediatric Gastroenterology, Hadassah Medical Organization and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9166100, Israel
- 4Department of Developmental Biology and Cancer Research, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9166100, Israel
- 5Department of Microbiology, Harvard Medical School, Boston, MA, USA
- 6Division of Infectious Diseases, Brigham & Women’s Hospital, Boston, MA, USA
- 7Department for Medical Biotechnology, The Technical University Berlin, Gustav-Meyer-Allee 25, 13355 Berlin, Germany
- 8Howard Hughes Medical Institute, Boston, MA, USA
Abstract
Host factors determine pathogen tropism but knowledge of host genes facilitating enteropathogenic Escherichia coli (EPEC) infection is limited. To identify host determinants required for infection by EPEC, we performed two independent genome-scale CRISPR-Cas9 screens. Both converged on host N-glycosylation as a critical requirement for infection. Genetic or pharmacological inhibition of N-glycan maturation revealed that N-glycosylation promotes infection through two distinct pathways. First, N-linked poly-N-acetyllactosamine glycans serve as receptors for the major EPEC adhesin, the bundle-forming pilus (BFP). Second, perturbation of N-glycosylation compromises host membrane structure, resulting in reduced type III secretion system activity, independently of host cell attachment. Using epithelial monolayers derived from human colon and jejunum organoids, we further show that EPEC attachment inversely correlates with terminal mannose exposure, suggesting glycan composition may be involved in determining intestinal tropism. Together, these findings establish host N-glycan maturation as a key host pathway exploited during enteric infection.
Related
- Claudin-2 protects from enteropathogenic E. coli-infection and colitis by promoting crypt fetalization via β1-integrin/FAK/YAP signaling
- In vitro and in vivo functional roles of three region 1 promoters in Escherichia coli K1 capsule gene cluster.
- Type 2 diabetes and the cardio–renal–metabolic syndrome: The evolving roles of GLP-1 and dual GLP-1/GIP receptor agonists
- Urgent Colectomy for Colonic Necrosis Following Shiga Toxin-Producing Escherichia coli O157 Infection in an Adult.
- Isolation, identification, and slow-growth phenotype characterization of a clinically derived Escherichia coli from urinary tract infection
BibTeX
@article{yaron2026dual,
title = {{Dual roles of host N-glycosylation in enteropathogenic Escherichia coli infection}},
author = {Klil Cohen Yaron and Yaakov Socol and Noam Yedidi and Michal Bejerano-Sagie and Miriam Ravins and Shira Fine-Leebhoff and Liron Birimberg-Schwartz and Myriam Grunewald and Karthik Hullahalli and Afonso de Sousa Vieira and Matthew K. Waldor and Sina Bartfeld and Sigal Ben-Yehuda and Ilan Rosenshine},
journal = {Cell Reports},
year = {2026},
month = sep,
doi = {10.1016/j.celrep.2026.118043},
url = {https://doi.org/10.1016/j.celrep.2026.118043},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Dual roles of host N-glycosylation in enteropathogenic Escherichia coli infection
AU - Klil Cohen Yaron
AU - Yaakov Socol
AU - Noam Yedidi
AU - Michal Bejerano-Sagie
AU - Miriam Ravins
AU - Shira Fine-Leebhoff
AU - Liron Birimberg-Schwartz
AU - Myriam Grunewald
AU - Karthik Hullahalli
AU - Afonso de Sousa Vieira
AU - Matthew K. Waldor
AU - Sina Bartfeld
AU - Sigal Ben-Yehuda
AU - Ilan Rosenshine
PY - 2026
DA - 2026/09/29
JO - Cell Reports
DO - 10.1016/j.celrep.2026.118043
UR - https://doi.org/10.1016/j.celrep.2026.118043
AB - Host factors determine pathogen tropism but knowledge of host genes facilitating enteropathogenic Escherichia coli (EPEC) infection is limited. To identify host determinants required for infection by EPEC, we performed two independent genome-scale CRISPR-Cas9 screens. Both converged on host N-glycosylation as a critical requirement for infection. Genetic or pharmacological inhibition of N-glycan maturation revealed that N-glycosylation promotes infection through two distinct pathways. First, N-linked poly-N-acetyllactosamine glycans serve as receptors for the major EPEC adhesin, the bundle-forming pilus (BFP). Second, perturbation of N-glycosylation compromises host membrane structure, resulting in reduced type III secretion system activity, independently of host cell attachment. Using epithelial monolayers derived from human colon and jejunum organoids, we further show that EPEC attachment inversely correlates with terminal mannose exposure, suggesting glycan composition may be involved in determining intestinal tropism. Together, these findings establish host N-glycan maturation as a key host pathway exploited during enteric infection.
SN - 2211-1247
ER -