Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway
Abstract Host cells contest invasion by intracellular bacterial pathogens with multiple strategies that recognise and/or damage the bacterial surface. To identify host defence factors targeted to intracellular bacteria, we developed a proximity biotinylation approach coupled to quantitative mass spectrometry that maps the host-bacterial interface during infection. Using this method, we discovered that intracellular Shigella and Salmonella become targeted by UFM1-protein ligase 1 (UFL1), an E3 ligase that catalyses the covalent attachment of Ubiquitin-fold modifier 1 (UFM1) to target substrates in a process called UFMylation. Shigella antagonises UFMylation in a dual manner: first, using its lipopolysaccharide to shield from UFL1 recruitment; second, preventing UFM1 decoration by the bacterial effector IpaH9.8. Absence of UFMylation leads to an increase of bacterial burden in human cells and zebrafish larvae. Contrary to ubiquitylation, the protective role of UFMylation is independent of autophagy. Altogether, our proximity mapping of the host-bacterial interface identifies UFMylation as an ancient antibacterial pathway and holds great promise to reveal other cell-autonomous immunity mechanisms.
Authors
- Serge Mostowy (ORCID: https://orcid.org/0000-0002-7286-6503)
- Hannah Painter (ORCID: https://orcid.org/0000-0003-0445-7473)
- Margarida C. Gomes (ORCID: https://orcid.org/0000-0001-9656-6145)
- Francis Impens (ORCID: https://orcid.org/0000-0003-2886-9616)
- Sydney L. Miles (ORCID: https://orcid.org/0000-0003-2291-4105)
- Fabien Théry (ORCID: https://orcid.org/0000-0001-5007-0371)
- Kathryn Wright (ORCID: https://orcid.org/0000-0001-6508-3386)
- Damián Lobato‐Márquez (ORCID: https://orcid.org/0000-0002-0044-7588)
- Eva‐Maria Frickel (ORCID: https://orcid.org/0000-0002-9515-3442)
- Jonathan N. Pruneda (ORCID: https://orcid.org/0000-0002-0304-4418)
- Lucas Jarche
- Gerbrand J. van der Heden van Noort (ORCID: https://orcid.org/0000-0001-5955-6431)
- John R. Rohde (ORCID: https://orcid.org/0000-0002-8569-3760)
- Ana T. López-Jiménez (ORCID: https://orcid.org/0000-0002-0289-738X)
- Dominik Brokatzky (ORCID: https://orcid.org/0000-0001-6304-3292)
- Shelby T. Hoffmeister
- Jeremy Benjamin
Institutions
- University of Geneva (CH)
- Dalhousie University (CA)
- Oregon Health & Science University (US)
- Leiden University Medical Center (NL)
- Ghent University (BE)
- London School of Hygiene & Tropical Medicine (GB)
- VIB-UGent Center for Medical Biotechnology (BE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-09-17
- DOI
- https://doi.org/10.1038/s41467-026-77860-y
- Primary Topic
- Biotin and Related Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- London School of Hygiene and Tropical Medicine
- European Commission
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Dalhousie University
- Centro Nacional de Biotecnología