Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway.
10 affiliations
- 1Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK. [email protected].
- 2Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland. [email protected].
- 3VIB-UGent Center for Medical Biotechnology, VIB, Ghent, Belgium.
- 4Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.
- 5Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK.
- 6Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon, USA.
- 7Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
- 8Department of Cell and Chemical Biology, Leiden University Medical Centre, Leiden, The Netherlands.
- 9Department of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland.
- 10Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, UK. [email protected].
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.
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BibTeX
@article{lopezjimenez2026proximity,
title = {{Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway.}},
author = {Ana T López-Jiménez and Fabien Théry and Kathryn Wright and Hannah Painter and Shelby T Hoffmeister and Lucas Jarche and Jeremy Benjamin and Gerbrand J van der Heden van Noort and Dominik Brokatzky and Margarida C Gomes and Sydney L Miles and Damián Lobato-Márquez and Eva-Maria Frickel and John Rohde and Jonathan N Pruneda and Francis Impens and Serge Mostowy},
journal = {Nature communications},
year = {2026},
month = sep,
doi = {10.1038/s41467-026-77860-y},
url = {https://europepmc.org/article/MED/42897205},
note = {CC BY},
}
RIS
TY - JOUR
TI - Proximity biotinylation at the host-Shigella interface reveals UFMylation as an antibacterial pathway.
AU - Ana T López-Jiménez
AU - Fabien Théry
AU - Kathryn Wright
AU - Hannah Painter
AU - Shelby T Hoffmeister
AU - Lucas Jarche
AU - Jeremy Benjamin
AU - Gerbrand J van der Heden van Noort
AU - Dominik Brokatzky
AU - Margarida C Gomes
AU - Sydney L Miles
AU - Damián Lobato-Márquez
AU - Eva-Maria Frickel
AU - John Rohde
AU - Jonathan N Pruneda
AU - Francis Impens
AU - Serge Mostowy
PY - 2026
DA - 2026/09/17
JO - Nature communications
DO - 10.1038/s41467-026-77860-y
UR - https://europepmc.org/article/MED/42897205
AB - 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.
SN - 2041-1723
ER -